A regulatory pathway model of neuropsychological disruption in Havana syndrome.

Introduction: In 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with brain injury. The etiology of these Anomalous Health Incidents (AHI) and subsequent symptoms remains unknown. This report investigates putative exposure-symptom pathology by assembling a network model of published bio-behavioral pathways and assessing how dysregulation of such pathways might explain loss of function in these subjects using data available in the published literature. Given similarities in presentation with mild traumatic brain injury (mTBI), we used the latter as a clinically relevant means of evaluating if the neuropsychological profiles observed in Havana Syndrome Havana Syndrome might be explained at least in part by a dysregulation of neurotransmission, neuro-inflammation, or both. Method: Automated text-mining of >9,000 publications produced a network consisting of 273 documented regulatory interactions linking 29 neuro-chemical markers with 9 neuropsychological constructs from the Brief Mood Survey, PTSD Checklist, and the Frontal Systems Behavior Scale. Analysis of information flow through this network produced a set of regulatory rules reconciling to within a 6% departure known mechanistic pathways with neuropsychological profiles in N = 6 subjects. Results: Predicted expression of neuro-chemical markers that jointly satisfy documented pathways and observed symptom profiles display characteristically elevated IL-1B, IL-10, NGF, and norepinephrine levels in the context of depressed BDNF, GDNF, IGF1, and glutamate expression (FDR < 5%). Elevations in CRH and IL-6 were also predicted unanimously across all subjects. Furthermore, simulations of neurological regulatory dynamics reveal subjects do not appear to be "locked in" persistent illness but rather appear to be engaged in a slow recovery trajectory. Discussion: This computational analysis of measured neuropsychological symptoms in Havana-based diplomats proposes that these AHI symptoms may be supported in part by disruption of known neuroimmune and neurotransmission regulatory mechanisms also associated with mTBI.

A Cross-sectional Cohort Study to Assess Long-term Neurocognitive and Psychiatric Symptoms of Mefloquine Use in Veterans.

INTRODUCTION: To evaluate the associations between neurocognitive and psychiatric health outcomes with mefloquine or any antimalarial exposure. MATERIALS AND METHODS: Medical records were systematically reviewed to identify veterans that indicated antimalarial medication use. Linear regression was performed to examine associations between mefloquine/antimalarial exposure and health outcomes. The mefloquine-exposed group was further compared with normative populations for the same health outcomes. RESULTS: In the adjusted models, no significant differences were noted between the two exposure groups and the unexposed group for any of the health measures (P-value > 0.05). When compared to normative population samples, the mefloquine-exposed group had poorer health and greater neurobehavioral symptom severity or cognitive complaints. CONCLUSION: This study suggests that mefloquine use by veterans referred for intensive evaluation of their military deployment exposures and health was not associated with increased, long-term, neurocognitive/psychiatric symptoms compared to unexposed veterans.

Compounding Effects of Traumatic Brain Injury, Military Status, and Other Factors on Pittsburgh Sleep Quality Index: A Meta-analysis.

INTRODUCTION: Traumatic brain injury (TBI) or concussion is a known risk factor for multiple adverse health outcomes, including disturbed sleep. Although prior studies show adverse effects of TBI on sleep quality, its compounding effect with other factors on sleep is unknown. This meta-analysis aimed to quantify the effects of TBI on subjective sleep quality in the context of military status and other demographic factors. MATERIALS AND METHODS: A programmatic search of PubMed database from inception to June 2020 was conducted to identify studies that compared subjective sleep quality measured using Pittsburgh Sleep Quality Index (PSQI) in individuals with TBI relative to a control group. The meta-analysis included group-wise standard mean difference (SMD) and 95% CI. Pooled means and SDs were obtained for TBI and non-TBI groups with and without military service, and meta-regression was conducted to test for group effects. Exploratory analysis was performed to test for the effect of TBI, non-head injury, military status, sex, and age on sleep quality across studies. RESULTS: Twenty-six articles were included, resulting in a combined total of 5,366 individuals (2,387 TBI and 2,979 controls). Overall, individuals with TBI self-reported poorer sleep quality compared to controls (SMD = 0.63, 95% CI: 0.45 to 0.80). Subgroup analysis revealed differences in the overall effect of TBI on PSQI, with a large effect observed in the civilian subgroup (SMD: 0.80, 95% CI: 0.57 to 1.03) and a medium effect in the civilian subgroup with orthopedic injuries (SMD: 0.40, 95% CI: 0.13 to 0.65) and military/veteran subgroup (SMD: 0.43, 95% CI: 0.14 to 0.71). Exploratory analysis revealed that age and history of military service significantly impacted global PSQI scores. CONCLUSIONS: Poor sleep quality in TBI cohorts may be due to the influence of multiple factors. Military/veteran samples had poorer sleep quality compared to civilians even in the absence of TBI, possibly reflecting unique stressors associated with prior military experiences and the sequelae of these stressors or other physical and/or psychological traumas that combine to heightened vulnerability. These findings suggest that military service members and veterans with TBI are particularly at a higher risk of poor sleep and its associated adverse health outcomes. Additional research is needed to identify potential exposures that may further heighten vulnerability toward poorer sleep quality in those with TBI across both civilian and military/veteran populations.

Influenza Vaccination, Self-reported Illness, and Obstacles for Vaccination Among the 2010 ROTC Warrior Forge Cadet Cohort.

INTRODUCTION: This study evaluates a large cohort of college students after the 2009-2010 pandemic H1N1 influenza season. The objective was to assess influenza vaccination status, influenzalike illnesses (ILIs), and other characteristics associated with attaining immunizations. METHODS: This study was conducted during the summer 2010 the Reserve Officer Training Corps Leadership Development and Assessment Course involving 6272 college students. A voluntary, anonymous questionnaire was administered to assess study objectives. RESULTS: Vaccination rates were 39.9% for pandemic H1N1, 40.6% for seasonal influenza, and 32.6% for receiving both vaccinations. Age less than 25 and having a Reserve Officer Training Corps scholarship were associated with lower odds of receiving vaccinations, whereas entering the nursing field and simultaneous membership in the Army reserve forces were associated with higher odds of vaccination. There are 11.2% of respondents reported having an ILI, including 4.3% with severe ILI. There were 4184 reasons indicated for not attaining influenza vaccinations, which are listed in categorical groupings. CONCLUSIONS: A historical anchor for vaccination rates and ILI is provided in a large cohort of college students following the 2009 H1N1 influenza pandemic. Influenza immunization locations were determined, as was self-reported obstacles to receiving vaccinations. These are important results for public health leaders seeking to increase vaccination rates during future influenza seasons.

Career Satisfaction of Military Medical Officers.

INTRODUCTION: Having a mentor is associated with higher job satisfaction among U.S. physicians. The objective of this study was to assess satisfaction among military medical officers and to assess if mentorship and job satisfaction are associated with intention to continue military service. MATERIALS AND METHODS: This is a cross-sectional study using voluntary, anonymous data from 2018 Uniformed Services Academy of Family Physicians Annual Meeting registered attendees who completed an online Omnibus Survey. Outcome measures: satisfaction with work hours and workload; voice in organizational decision-making; amount of teaching, research, and other administrative tasks; being and having a mentor; and likelihood of remaining in the military beyond current service obligation. Statistical analysis: descriptive statistics, chi-square, and logistic regression. RESULTS: There was a 66% response rate (310/568) among registered attendees. Respondents reported being satisfied with work hours-workload (53.3%), voice in organizational decision-making (47.4%), and amount of teaching-research-other administrative tasks (55.7%). About 64.6% of respondents reported being a mentor, and 80.7% reported having a mentor. About 53.4% reported being likely/very likely to continue military service beyond their current service obligation. Adjustment for demographic and occupational factors, with significance defined as P ≤ 0.05, revealed that higher percent time in clinical care was negatively associated with satisfaction with voice in organizational decision-making; being a mentor and working in an academic practice setting were positively associated with satisfaction in amount of time with teaching, research, and administrative tasks; and having a mentor was the only factor associated with being likely/very likely to continue military service beyond current service obligation (odd ratio 3.9, 95% confidence interval 1.2-12.1). CONCLUSIONS: Having a mentor was the only factor associated with intention to remain in the military among 2018 Uniformed Services Academy of Family Physicians Omnibus Survey respondents. These results support enhancing mentorship among military medical officers.

A Cluster of Exertional Rhabdomyolysis Cases in a ROTC Program Engaged in an Extreme Exercise Program.

Exertional rhabdomyolysis (ER) is on the rise among service members and high school and college athletes. Reported risk factors for ER include fitness level, sudden increase in exercise intensity and duration, and eccentric predominant exercise. This study examined an ER cluster among Reserve Officer Training Corps cadets who participated in a mandatory, timed, extreme conditioning program (ECP) workout. Forty-four cadets participated in this ECP; 11 were subsequently hospitalized with ER. Thirty-five cadets, including all who developed ER, completed a questionnaire to assess ECP times, prior fitness scores, and other ER risk factors. Cadets completed the ECP workout as individuals or in teams. Nine of 25 (36%) individual and two of 10 (20%) team participants were hospitalized with ER. Among the cadets, no associations were noted between hospitalization for ER and finish time, previous fitness scores, or dietary supplement use. The relative risk of developing ER was significantly increased in those who consumed alcohol in the week preceding the ECP (RR = 4.20; 95% CI 1.95, 9.03). In this cohort of Reserve Officer Training Corps cadets, an ECP resulted in a high rate of hospitalization for ER. Contrary to reported ER risk factors, higher baseline fitness was not protective. Rather, cadet knowledge that ECP performance was strongly linked to final cadet ranking greatly influenced intensity of effort.

Pulmonary artery dissection leading to cardiac tamponade as a cause of maternal death in a woman with pulmonary hypertension: a case report.

BACKGROUND: Severe pulmonary hypertension in pregnancy is known to carry a 40% risk of death for the mother. The most common cause of death in cases of pulmonary hypertension is heart failure. CASE: We present a case of maternal death due to dissection of the pulmonary artery resulting in cardiac tamponade. CONCLUSION: The sudden onset of severe chest pain radiating to the back should alert the clinician to the possibility of pulmonary artery dissection in pregnant patients with pulmonary hypertension. Severe chest pain may not be accompanied by changes in vital signs or oxygen saturation. Immediate delivery should be considered. However, delivery may worsen the mother's condition due to postpartum cardiovascular changes.

Does diabetes hide osteoarthritis pain?

Clinical practice and research efforts related to the highly prevalent and disabling disease, osteoarthritis (OA), have long been hampered by an inadequate case definition. Much of the difficulty is due to a lack of agreement between X-rays evidence of OA and a patient's report of pain at that site. Such discordance between reported pain and radiographic evidence of OA has been attributed to several factors. This paper proposes another possible explanation, for at least a portion of such patients. It is hypothesized that an insidiously increasing diabetic neuropathy, particularly in the lower extremity, while first causing some pain, may gradually inhibit the ability to feel pain which might have otherwise been reported by those patients without neuropathy. Many of these patients with early stage glucose dysmetabolism will proceed to develop overt type 2 diabetes; however, the pain-inhibiting neuropathy caused by glucose metabolism dysfunction may manifest long before such a diagnosis. The high prevalence of diabetes and pre-diabetic conditions, especially among the aged population, could mean that a substantial number of individuals with osteoarthritis will have both diseases to varying degrees over time. Validating and quantifying this hypothesized association would be useful to millions of persons and would significantly impact both research and clinical practice dealing with these major diseases of older persons.

Validating the use of ICD-9-CM codes to evaluate gestational age and birth weight.

BACKGROUND: Efforts to reduce preterm and low-weight births are among the leading public health objectives in the United States and the world. A necessary component of any public health endeavor is surveillance. The Department of Defense (DoD) Birth and Infant Health Registry (Registry) uses electronic healthcare utilization data to assess reproductive health outcomes among military families. Infant health outcomes are coded using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). The objective of this study was to determine the accuracy of using electronically derived ICD-9-CM codes for assessing gestational age and birth weight among Registry infants compared to medical records. METHODS: The authors assessed birth outcome agreement by comparing electronic Registry data for infants born at military treatment facilities (MTFs) from 1999-2002 and 1,858 randomly selected birth medical records from 17 MTFs, with descriptive statistics and measures of agreement, including the kappa statistic. RESULTS: Of the 1,858 reviewed infant records, 1,669 were successfully matched to the Registry analytic dataset for analyses. Despite small differences in parental demographics, this investigation established "near perfect" agreement for the primary outcomes: kappa of 0.83 for preterm and 0.87 for low birth weight. Subgroup analyses revealed no significant differences in gestational age and birth-weight agreement based on the presence of a birth defect, military parent rank, branch of military service, or specific hospital characteristics. CONCLUSIONS: Electronically derived ICD-9-CM codes provide an accurate assessment of the gestational age and low birth weight reflected in the birth medical records of infants in a large birth and infant health registry. These findings support the integrity of Registry data for investigations assessing preterm and low-weight births among U.S. service member families.

Phase conjugation and negative refraction using nonlinear active metamaterials.

We present an experimental demonstration of phase conjugation using nonlinear metamaterial elements. Active split-ring resonators loaded with varactor diodes are demonstrated theoretically to act as phase-conjugating or time-reversing discrete elements when parametrically pumped and illuminated with appropriate frequencies. The metamaterial elements were fabricated and shown experimentally to produce a time-reversed signal. Measurements confirm that a discrete array of phase-conjugating elements act as a negatively refracting time-reversal rf lens only 0.12λ thick.

Respiratory illnesses at the 2009 U.S. Army ROTC Advanced Camp.

Every summer the U.S. Army Reserve Officer Training Corps (ROTC) conducts the Leader Development Assessment Course (LDAC) for several thousand upcoming senior-year cadets. This study describes respiratory illnesses at 2009 ROTC LDAC after the emergence of the novel H1N1 influenza pandemic. This retrospective cohort study examines 5554 cadets and 1,616 cadres from 2009, and 5180 LDAC 2008 cadets. Respiratory clinic visits for 2009 cadets were higher than 2009 cadres and 2008 cadets, at 8.7, 2.0, and 4.2 visits per 1000 person-days available, respectively (p < 0.001). Further, respiratory illness hospitalizations and isolations were higher for 2009 cadets than cadres (p = 0.020). Although substantial efforts were made to prevent respiratory infections, there was considerable impact from respiratory illnesses, in the context of the novel H1N1 influenza pandemic, among 2009 ROTC LDAC participants. Our experience offers important lessons for future LDAC planning and for similar close quarters living circumstances.

Exercise and osteoarthritis: are we stopping too early? findings from the Clearwater Exercise Study.

The value of exercise for people with knee osteoarthritis (OA) receives continuing consideration. The optimal length of study follow-up time remains unclear. A group of individuals with knee OA participating in an exercise intervention was followed for 2 years. The authors quantified the change in knee-pain scores during Months 1-12 and during Months 13-24. Eleven individuals with radiographic knee OA and knee-pain scores of 2+ were evaluated. Pain scores were collected weekly from participants who exercised three times a week. Participants demonstrated pain reduction during both time periods. Pain reduction during Months 13-24, -10.7%, was slightly higher than pain reduction during Months 1-12, -7.8%. Among people with knee OA who exercise, these findings suggest that knee-pain amelioration continues beyond 12 months. Clinicians should consider encouraging long-term exercise programs for knee-OA patients. To best characterize the effect of exercise on knee pain, researchers designing clinical trials might want to lengthen the studies' duration.

Effect of regular exercise on the radiographic progression of foot osteoarthritis.

Among the elderly, osteoarthritis often causes chronic pain and disability. Although research has addressed the association between exercise and osteoarthritis, few studies have examined the effect of exercise on the radiographic progression of osteoarthritis. We investigated the relationship between ongoing exercise and radiographic progression of foot osteoarthritis. The first metatarsophalangeal and medial cuneiform-first tarsometatarsal joints were assessed. Joint-specific osteoarthritis radiographic progression scores were determined using four assessments: joint space narrowing, osteophytes, sclerosis, and a composite score. This cohort study included a subset of 221 men and women aged 40 to 91 years participating in a community-based osteoarthritis study. Adjusted risk estimates (95% confidence intervals) summarizing the relationship between ongoing exercise and radiographic progression in the first metatarsophalangeal joint ranged from 0.34 (0.11-0.99) for osteophytes to 0.66 (0.23-1.92) for sclerosis; because only eight individuals experienced medial cuneiform-first tarsometatarsal joint progression, these estimates were less stable, ranging from 2.41 (0.49-11.83) for composite to 4.29 (0.11-166.52) for osteophytes. Overall, our findings do not suggest that regular exercise is a risk factor for foot osteoarthritis progression. Future replication studies are warranted to confirm these findings.

The association between medication usage and dropout status among participants of an exercise study for people with osteoarthritis.

BACKGROUND AND PURPOSE: Little is known about predictors of dropout status in exercise studies for people with osteoarthritis. Losses to follow-up can pose serious threats to study validity. The purpose of this study was to assess the ability of arthritis medication usage the month prior to enrollment to predict dropout status among participants in an exercise study for people with osteoarthritis. SUBJECTS AND METHODS: Men and women who participated in an exercise study for people with osteoarthritis (N=143) were followed. Participants who completed 24+ months of the exercise program were considered retained, whereas individuals who withdrew prior to 24 months were considered dropouts. RESULTS: Of the 143 participants analyzed, 78 (55%) completed 24+ months of the exercise program and 65 (45%) dropped out. Among those who reported arthritis medication usage, 54% were lost to follow-up. The group reporting no usage of arthritis medication had a 20% dropout rate (odds ratio=3.5, 95% confidence interval=1.6-7.6). The final adjusted model controlling for baseline health status, body mass index, and the interaction between baseline health status and body mass index indicated that those individuals who reported arthritis medication usage were more than 4 times more likely to drop out than were those who reported no arthritis medication usage (odds ratio=4.5, 95% confidence interval=1.8-11.4). DISCUSSION AND CONCLUSION: The results showed that self-reported arthritis medication usage the month prior to study enrollment was associated with subsequent dropout status among this group of exercisers with osteoarthritis. Further identification of baseline characteristics predictive of participant dropout status may benefit future exercise studies. A priori knowledge of "at-risk" exercise study participants will afford the opportunity for the timely allocation of appropriate resources aimed at reducing losses to follow-up.