Challenges to the central nervous system during human spaceflight missions to Mars.

Space travel presents a number of environmental challenges to the central nervous system, including changes in gravitational acceleration that alter the terrestrial synergies between perception and action, galactic cosmic radiation that can damage sensitive neurons and structures, and multiple factors (isolation, confinement, altered atmosphere, and mission parameters, including distance from Earth) that can affect cognition and behavior. Travelers to Mars will be exposed to these environmental challenges for up to 3 years, and space-faring nations continue to direct vigorous research investments to help elucidate and mitigate the consequences of these long-duration exposures. This article reviews the findings of more than 50 years of space-related neuroscience research on humans and animals exposed to spaceflight or analogs of spaceflight environments, and projects the implications and the forward work necessary to ensure successful Mars missions. It also reviews fundamental neurophysiology responses that will help us understand and maintain human health and performance on Earth.

Female mice are protected from space radiation-induced maladaptive responses.

Interplanetary exploration will be humankind's most ambitious expedition and the journey required to do so, is as intimidating as it is intrepid. One major obstacle for successful deep space travel is the possible negative effects of galactic cosmic radiation (GCR) exposure. Here, we investigate for the first time how combined GCR impacts long-term behavioral and cellular responses in male and female mice. We find that a single exposure to simulated GCR induces long-term cognitive and behavioral deficits only in the male cohorts. GCR exposed male animals have diminished social interaction, increased anxiety-like phenotype and impaired recognition memory. Remarkably, we find that the female cohorts did not display any cognitive or behavioral deficits after GCR exposure. Mechanistically, the maladaptive behavioral responses observed only in the male cohorts correspond with microglia activation and synaptic loss in the hippocampus, a brain region involved in the cognitive domains reported here. Furthermore, we measured reductions in AMPA expressing synaptic terminals in the hippocampus. No changes in any of the molecular markers measured here are observed in the females. Taken together these findings suggest that GCR exposure can regulate microglia activity and alter synaptic architecture, which in turn leads to a range of cognitive alterations in a sex dependent manner. These results identify sex-dependent differences in behavioral and cognitive domains revealing promising cellular and molecular intervention targets to reduce GCR-induced chronic cognitive deficits thereby boosting chances of success for humans in deep space missions such as the upcoming Mars voyage.

Angiopoietin-4 increases permeability of blood vessels and promotes lymphatic dilation.

The angiopoietin (Ang) ligands are potential therapeutic targets for lymphatic related diseases, which include lymphedema and cancer. Ang-1 and Ang-2 functions are established, but those of Ang-4 are poorly understood. We used intravital fluorescence microscopy to characterize Ang-4 actions on T241 murine fibrosarcoma-associated vessels in mice. The diameters of lymphatic vessels draining Ang-4- or VEGF-C (positive control)-expressing tumors increased to 123 and 135 µm, respectively, and parental, mock-transduced (negative controls) and tumors expressing Ang-1 or Ang-2 remained at baseline (∼60 µm). Ang-4 decreased human dermal lymphatic endothelial cell (LEC) monolayer permeability by 27% while increasing human dermal blood endothelial cell (BEC) monolayer permeability by 200%. In vivo, Ang-4 stimulated a 4.5-fold increase in tumor-associated blood vessel permeability compared with control when measured using intravital quantitative multiphoton microscopy. Ang-4 activated receptor signaling in both LECs and BECs, evidenced by tyrosine kinase with Ig and endothelial growth factor homology domains-2 (TIE2) receptor, protein kinase B, and Erk1,2 phosphorylation detectable by immunoblotting. These data suggest that Ang-4 actions are mediated through cell-type-specific networks and that lymphatic vessel dilation occurs secondarily to increased vascular leakage. Ang-4 also promoted survival of LECs. Thus, blocking Ang-4 may prune the draining lymphatic vasculature and decrease interstitial fluid pressure (IFP) by reducing vascular permeability.

Routine aspiration thrombectomy improves the diagnosis and management of embolic myocardial infarction.

OBJECTIVES: Assess the effect of aspiration thrombectomy on diagnosis and management of embolic acute myocardial infarction. BACKGROUND: Discrimination of embolic acute myocardial infarction from atherosclerotic plaque rupture/erosion prompts oral anticoagulation treatment of source of embolus, as well as avoiding unnecessary stenting and dual antiplatelet therapy. However, detection is difficult without aspiration. METHODS: We compared rates of diagnosis of embolic infarction for 2.5 years prior to (pre-RAT) and 2.5 years post routine aspiration thrombectomy (post-RAT). Baseline demographics, outcomes, and treatment strategies were also compared between the embolic infarction and atherosclerotic infarction. RESULTS: Diagnosed embolic infarction rose from 1.2% in the pre-RAT era to 2.8% in the post-RAT period (P < 0.05). In addition, more successful removal of thrombus by aspiration led to less stenting (20% vs. 55% P < 0.05) in the post-RAT period thus avoiding the hazards of "triple therapy." Embolic infarction was more frequently associated with atrial fibrillation (55% vs. 8%), had higher mortality (17% vs. 4%), and had higher rates of embolic stroke (13% vs. 0.3%) when compared with atherosclerotic MI (all P < 0.05). CONCLUSIONS: Routine aspiration thrombectomy more readily identifies embolic infarction allowing more specific therapy and avoidance of stenting and triple anticoagulant therapy.

Densely ionizing radiation affects DNA methylation of selective LINE-1 elements.

Long Interspersed Nucleotide Element 1 (LINE-1) retrotransposons are heavily methylated and are the most abundant transposable elements in mammalian genomes. Here, we investigated the differential DNA methylation within the LINE-1 under normal conditions and in response to environmentally relevant doses of sparsely and densely ionizing radiation. We demonstrate that DNA methylation of LINE-1 elements in the lungs of C57BL6 mice is dependent on their evolutionary age, where the elder age of the element is associated with the lower extent of DNA methylation. Exposure to 5-aza-2'-deoxycytidine and methionine-deficient diet affected DNA methylation of selective LINE-1 elements in an age- and promoter type-dependent manner. Exposure to densely IR, but not sparsely IR, resulted in DNA hypermethylation of older LINE-1 elements, while the DNA methylation of evolutionary younger elements remained mostly unchanged. We also demonstrate that exposure to densely IR increased mRNA and protein levels of LINE-1 via the loss of the histone H3K9 dimethylation and an increase in the H3K4 trimethylation at the LINE-1 5'-untranslated region, independently of DNA methylation. Our findings suggest that DNA methylation is important for regulation of LINE-1 expression under normal conditions, but histone modifications may dictate the transcriptional activity of LINE-1 in response to exposure to densely IR.

Cellular effects of acute exposure to high peak power microwave systems: Morphology and toxicology.

Electric fields produced by advanced pulsed microwave transmitter technology now readily exceed the Institute of Electrical and Electronic Engineers (IEEE) C.95.1 peak E-field limit of 100 kV/m, highlighting a need for scientific validation of such a specific limit. Toward this goal, we exposed Jurkat Clone E-6 human lymphocyte preparations to 20 high peak power microwave (HPPM) pulses (120 ns duration) with a mean peak amplitude of 2.3 MV/m and standard deviation of 0.1 with the electric field at cells predicted to range from 0.46 to 2.7 MV/m, well in excess of current standard limit. We observed that membrane integrity and cell morphology remained unchanged 4 h after exposure and cell survival 24 h after exposure was not statistically different from sham exposure or control samples. Using flow cytometry to analyze membrane disruption and morphological changes per exposed cell, no changes were observed in HPPM-exposed samples. Current IEEE C95.1-2005 standards for pulsed radiofrequency exposure limits peak electric field to 100 kV/m for pulses shorter than 100 ms [IEEE (1995) PC95.1-Standard for Safety Levels with Respect to Human Exposure to Electric, Magnetic and Electromagnetic Fields, 0 Hz to 300 GHz, Institute of Electrical and Electronic Engineers: Piscataway, NJ, USA]. This may impose large exclusion zones that limit HPPM technology use. In this study, we offer evidence that maximum permissible exposure of 100 kV/m for peak electric field may be unnecessarily restrictive for HPPM devices. Bioelectromagnetics. 37:141-151, 2016. © 2016 Wiley Periodicals, Inc.

Outcomes in the treatment of periprosthetic joint infection after shoulder arthroplasty: a systematic review.

BACKGROUND: Although many case series have been published on the treatment of shoulder periprosthetic joint infection (PJI), few provide direct comparison of outcomes. This systematic review synthesizes the available English literature on shoulder PJI to quantify treatment effectiveness. METHODS: The PubMed and Embase databases were searched in April 2014. Keywords included "shoulder replacement infection" and "shoulder arthroplasty infection." Of 663 titles, 55 manuscripts underwent full-text review after application of exclusion criteria. Thirty articles were finally included. RESULTS: Propionibacterium acnes was most commonly reported, representing 38.9% of infections, followed by Staphylococcus species. Risk factors for shoulder PJI include previous surgery, increased age, male gender, increased body mass index, and diabetes mellitus. The average white blood cell count in 13 studies was 7472 cells/µL. Ten studies reported a mean erythrocyte sedimentation rate of 27.6 mm/h, whereas 14 studies reported a mean C-reactive protein level of 2.6 mg/dL. P. acnes in intraoperative culture specimens was an independent risk factor for failed treatment for shoulder PJI. When outcomes were pooled, no statistical difference was found in the success rates of 1-stage, 2-stage, or resection arthroplasty revision; each displayed a success rate >90%. However, single-stage revision produced the highest mean Constant score; implant retention resulted in the best range of motion. CONCLUSIONS: Our data suggest that single-stage revision can be as effective as 2-stage or resection treatments; however, the retrospective nature of these data precluded our ability to control for confounding variables. Future studies on shoulder PJI should involve direct comparisons of 1-stage vs. 2-stage treatment while comparing cost, morbidity, and functional outcomes.

Outcomes by day and night for patients bypassing the emergency department presenting with ST-segment elevation myocardial infarction identified with a pre-hospital electrocardiogram.

BACKGROUND: Pre-hospital ECG and emergency department (ED) bypass direct to the catheter laboratory may optimize reperfusion times for patients with ST-segment elevation myocardial infarction. Questions remain over feasibility and safety during off hours. AIMS: To determine if presenting time of day is associated with differences in in-hospital and 30-day mortality and key reperfusion times. METHODS/RESULTS: Seven hundred and twenty consecutive patients with STEMI triaged directly from the field to the catheter laboratory between June 2004-May 2013. Vital status was reported as of August 2013. The mean age was 65 ± 14 years, and 75.1% were male. Overall mortality (in-hospital/30 days) did not significantly differ for patients (3.4% in hours and 3.1% off hours; P = N/S). Symptom onset-to-arrival to the heart attack was non-significantly lower (100 minutes off hours (IQR 78-174) versus 110 minutes in hours (IQR 75-199), P = N/S). Call-to-balloon time was not significantly affected by the time of presentation: 150 min in hours (IQR 111-239) versus 154 minutes during off hours (IQR 115-225) P = N/S. Overall door-to-balloon time was 36 minutes (IQR 25-51), 34 minutes in hours (IQR 24-49) versus 40 minutes off hours (IQR 29-55) P = N/S. The overall false positive activation rate was only 13.1%, (in hours 12.2% vs. off hours 14.6%, respectively, P = N/S). CONCLUSIONS: In a unit with an established field triage system facilitating ED bypass, reperfusion times and mortality are not significantly influenced by whether the patient presents during standard working hours or outside of these hours.

Leukocyte esterase in the diagnosis of shoulder periprosthetic joint infection.

BACKGROUND: Shoulder periprosthetic joint infection (PJI) is difficult to diagnose with traditional methods. Leukocyte esterase (LE) has recently proven to be reliable in knee arthroplasty; however, its value in the shoulder has not been explored. We hypothesized that LE would display high sensitivity and specificity in shoulder PJI. METHODS: Two groups were prospectively evaluated: 45 primary and 40 revision shoulder arthroplasties. Synovial fluid and soft tissue cultures were obtained at surgery. Synovial fluid was evaluated with LE test strips. Any aspiration that contained erythrocytes was centrifuged and retested. Shoulder PJI was defined by modified Musculoskeletal Infection Society (MSIS) criteria. RESULTS: Of 5 primaries with positive tissue cultures (11%), only 1 was positive for LE. Of 16 revisions with positive cultures (40%), 4 had positive LE results. Among all patients with bacterial isolates, 6 aspirates were not interpretable (29%), despite centrifugation. LE had sensitivity of 25% and specificity of 75% to predict positive cultures in revisions. Ten revision patients met modified MSIS criteria for PJI. The sensitivity of LE in these patients was 30%, and the specificity was 67% (positive predictive value, 43%; negative predictive value, 83%). If bloody aspirates were considered positive, LE sensitivity in MSIS PJI increased to 60%, but the positive predictive value fell to 37.5%. CONCLUSION: LE is an unreliable diagnostic measure in shoulder PJI. The presence of erythrocytes within aspirates further decreased its accuracy. We conclude that LE should not be used for the routine identification of shoulder PJI.

Pectoralis major tendon transfer for irreparable subscapularis tears.

BACKGROUND: Subscapularis insufficiency is a debilitating condition with few treatment options. Historically, pectoralis major tendon transfer has been suggested when the subscapularis tendon or muscle is deemed irreparable; however, the results of this salvage procedure have been mixed. METHODS: A comprehensive review of the peer-reviewed literature addressing pectoralis major tendon transfers was performed. The clinical presentation, relevant anatomy, biomechanical rationale, surgical indications, technical considerations, reported outcomes, and significant complications are reviewed in this report. Where possible, attempts at direct comparison of outcomes among surgical techniques and surgical indications have been made. RESULTS AND CONCLUSIONS: Despite the heterogeneous reporting of clinical results, it is clear that surgical indications affect outcomes. Specifically, isolated subscapularis insufficiency shows the best prognosis with pectoralis major tendon transfer. Patients with anterosuperior instability after large rotator cuff tears or shoulder arthroplasty have the least predictable pain relief and worse functional outcomes. LEVEL OF EVIDENCE: Review article.

Elbow arthroscopy: early complications and associated risk factors.

BACKGROUND: Elbow arthroscopy is increasingly used to treat complex pathology. The purpose of this study was to investigate early complication rates after elbow arthroscopy and identify risk factors for adverse events. METHODS: Consecutive elbow arthroscopies performed during a 13-year period were reviewed, identifying early perioperative complications. Major complications included deep infection, permanent nerve injury, or complications requiring additional anesthesia. Minor complications included superficial wound complications and transient nerve palsies. Complications were compared with a surgical complexity scale based on the procedure performed, the number of arthroscopic portals, and tourniquet time. RESULTS: Of 417 procedures, there were 37 minor (8.9%) and 20 major (4.8%) complications. The rates of superficial and deep infections were 6.7% and 2.2%, respectively. Major complications included 9 deep infections, 6 cases of heterotopic ossification requiring further surgery, and 4 manipulations under anesthesia. There were 7 transient sensory nerve complications, and no motor deficits. No differences in complication rates were seen between low-, moderate-, and high-complexity (10.2%, 16.3% and 14.4%, respectively) cases. Intraoperative steroid injections were strongly associated with postoperative superficial (14.1% vs 2.0%) and deep infection (4.9% vs 0.4%) in elbows receiving vs those not receiving steroid (P < .0001). CONCLUSIONS: Complications of elbow arthroscopy are seen in approximately 14% of cases. Most complications are minor, not affecting clinical outcome. Major complications occur in 5% of cases, often requiring repeat surgery. Intraoperative postsurgical steroid injections are associated with increased risk of perioperative infections. Case complexity does not appear to affect the rate of complications with modern surgical techniques.

Effects of proton and oxygen ion irradiation on cardiovascular function and structure in a rabbit model.

PURPOSE: Astronauts on missions beyond low Earth orbit will be exposed to galactic cosmic radiation, and there is concern about potential adverse cardiovascular effects. Most of the research to identify cardiovascular risk of space radiation has been performed in rodent models. To aid in the translation of research results to humans, the current study identified long-term effects of high-energy charged particle irradiation on cardiovascular function and structure in a larger non-rodent animal model. MATERIALS AND METHODS: At the age of 12 months, male New Zealand white rabbits were exposed to whole-body protons (250 MeV) or oxygen ions (16O, 600 MeV/n) at a dose of 0 or 0.5 Gy and were followed for 12 months after irradiation. Ultrasonography was used to measure in vivo cardiac function and blood flow parameters at 10- and 12-months post-irradiation. At 12 months after irradiation, blood cell counts and blood chemistry values were assessed, and cardiac tissue and aorta were collected for histological as well as molecular and biochemical analyses. Plasma was used for metabolomic analysis and to quantify common markers of cardiac injury. RESULTS: A small but significant decrease in the percentage of circulating lymphocytes and an increase in neutrophil percentage was seen 12 months after 0.5 Gy protons, while 16O exposure resulted in an increase in monocyte percentage. Markers of cardiac injury, cardiac troponin I (cTnI) and N-Terminal pro-B-type Natriuretic Peptide were modestly increased in the proton group, and cTnI was also increased after 16O. On the other hand, metabolomics on plasma at 12 months revealed no changes. Both types of irradiation demonstrated alterations in cardiac mitochondrial morphology and an increase in left ventricular protein levels of inflammatory cell marker CD68. However, changes in cardiac function were only mild. CONCLUSION: Low dose charged particle irradiation caused mild long-term changes in inflammatory markers, cardiac function, and structure in the rabbit heart, in line with previous studies in mouse and rat models.

Angiographic predictors of coronary hemodynamics.

Aims: Assess the correlation between diameter stenosis, lesion length, location, diffuse coronary disease and with fractional flow reserve (FFR). Methods/Results: We performed quantitative coronary analysis analysis on 384 lesions with stable coronary artery disease undergoing FFR assessment. Vessels were 59.1% left anterior descending artery (LAD), 16.1% left circumflex artery and 14.8% right coronary artery. Median diameter stenosis was 58% ± 2.5 and median lesion length was 10 mm ± 7.36. 21% of vessels were diffusely diseased. Lesions were 33.6% proximal, 44% mid-vessel and 12% distal. Median FFR was 0.85. Diameter stenosis correlated with lower FFR (p < 0.005, odds ratio [OR]: 2.4 [95% CI: 0.99-5.63]). There was no association between lesion length, location, number of proximal side branches and FFR. Vessels with diffuse disease had a nonsignificant trend for lower FFR (0.84 vs 0.85, p = 0.375, OR: 1.26 [95% CI: 0.76-2.09]). LAD lesions had significantly lower FFR compared with non-LAD (p < 0.001, OR: 2.55 [95% CI: 1.61-4.04]); including left circumflex artery and right coronary artery lesions (p = 0.001, OR: 3.4 [95% CI: 1.7-6.9]) and p = 0.02, OR: 2.55 [95% CI: 1.17-4.34]). Conclusion: FFR is not related to lesion length, location or number of proximal branches.

Ionizing radiation, cerebrovascular disease, and consequent dementia: A review and proposed framework relevant to space radiation exposure.

Space exploration requires the characterization and management or mitigation of a variety of human health risks. Exposure to space radiation is one of the main health concerns because it has the potential to increase the risk of cancer, cardiovascular disease, and both acute and late neurodegeneration. Space radiation-induced decrements to the vascular system may impact the risk for cerebrovascular disease and consequent dementia. These risks may be independent or synergistic with direct damage to central nervous system tissues. The purpose of this work is to review epidemiological and experimental data regarding the impact of low-to-moderate dose ionizing radiation on the central nervous system and the cerebrovascular system. A proposed framework outlines how space radiation-induced effects on the vasculature may increase risk for both cerebrovascular dysfunction and neural and cognitive adverse outcomes. The results of this work suggest that there are multiple processes by which ionizing radiation exposure may impact cerebrovascular function including increases in oxidative stress, neuroinflammation, endothelial cell dysfunction, arterial stiffening, atherosclerosis, and cerebral amyloid angiopathy. Cerebrovascular adverse outcomes may also promote neural and cognitive adverse outcomes. However, there are many gaps in both the human and preclinical evidence base regarding the long-term impact of ionizing radiation exposure on brain health due to heterogeneity in both exposures and outcomes. The unique composition of the space radiation environment makes the translation of the evidence base from terrestrial exposures to space exposures difficult. Additional investigation and understanding of the impact of low-to-moderate doses of ionizing radiation including high (H) atomic number (Z) and energy (E) (HZE) ions on the cerebrovascular system is needed. Furthermore, investigation of how decrements in vascular systems may contribute to development of neurodegenerative diseases in independent or synergistic pathways is important for protecting the long-term health of astronauts.

Ionizing Radiation and Bone Loss: Space Exploration and Clinical Therapy Applications.

Damage to normal, nontumor bone tissue following therapeutic irradiation increases the risk of fracture among cancer patients. For example, women treated for various pelvic tumors have been shown to have a greater than 65% increased incidence of hip fracture by 5 years postradiotherapy. Another practical situation in which exposure to ionizing radiation may negatively impact skeletal integrity is during extended spaceflight missions. There is a limited understanding of how spaceflight-relevant doses and types of radiation can influence astronaut bone health, particularly when combined with the significant effects of mechanical unloading experienced in microgravity. Historically, negative effects on osteoblasts have been studied. Radiation exposure has been shown to damage osteoblast precursors. Damage to local vasculature has been observed, ranging from decreased lumen diameter to complete ablation within the irradiated volume, causing a state of hypoxia. These effects result in suppression of bone formation and a general state of low bone turnover. More recently, however, we have demonstrated in pre-clinical mouse models, a very rapid but transient increase in osteoclast activity after exposure to spaceflight and clinically relevant radiation doses. Combined with long-term suppression of bone formation, this skeletal damage may cause long-term deficits. This review will present a broad set of literature outlining our current set knowledge of both clinical therapy and space exploration exposure to ionizing radiation. Additionally, we will discuss prevention of the initial osteoclast-mediated bone loss, the need to promote normal bone turnover and long-term quality of bone tissue, and our hypothesized molecular mechanisms.

Space Radiation and Bone Loss.

Exposure to ionizing radiation may negatively impact skeletal integrity during extended spaceflight missions to the moon, Mars, or near-Earth asteroids. However, our understanding of the effects of radiation on bone is limited when compared to the effects of weightlessness. In addition to microgravity, astronauts will be exposed to space radiation from solar and cosmic sources. Historically, radiation exposure has been shown to damage both osteoblast precursors and local vasculature within the irradiated volume. The resulting suppression of bone formation and a general state of low bone-turnover is thought to be the primary contributor to bone loss and eventual fracture. Recent investigations using mouse models have identified a rapid, but transient, increase in osteoclast activity immediately after irradiation with both spaceflight and clinically-relevant radiation qualities and doses. Together with a chronic suppression of bone formation after radiation exposure, this acute skeletal damage may contribute to long-term deterioration of bone quality, potentially increasing fracture risk. Direct evidence for the damaging effects of radiation on human bone are primarily demonstrated by the increased incidence of fractures at sites that absorb high doses of radiation during cancer therapy: exposures are considerably higher than what could be expected during spaceflight. However, both the rapidity of bone damage and the chronic nature of the changes appear similar between exposure scenarios. This review will outline our current knowledge of space and clinical exploration exposure to ionizing radiation on skeletal health.

Phase 2 study examining magnesium-dependent tinnitus.

BACKGROUND: Recent studies in noise-induced and idiopathic sensorineural hearing loss have suggested that magnesium supplementation may lessen both hearing loss and the severity of tinnitus in patients. Further epidemiological evidence indicates that all age groups of Americans fall short of the recommended daily allowance for magnesium by 100 mg daily. PURPOSE: The purpose of this study was to examine any potential benefit in lessening the severity of tinnitus in patients taking supplemental magnesium. RESEARCH DESIGN: The study was a single-arm, open-label, before-and-after study of oral magnesium (532 mg per day) in 26 patients for 3 months. Tinnitus severity was evaluated and recorded daily by the patient using the Tinnitus Distress Rating (TDR) scale of 0 (no tinnitus) to 10 (worst possible tinnitus). The Tinnitus Handicap Inventory (THI) was administered before and at the end of the study, and scores were converted to the grades of the 5-item Tinnitus Severity Scale (TSS). The purpose of this phase 2 study was to investigate whether the treatment was effective at all, and, as such, a placebo control was not performed. All data were collected at Mayo Clinic in Scottsdale, Arizona, between March 6 and December 10, 2008. STUDY SAMPLE: Patients with moderate to very severe tinnitus (TDR score of 3 through 8). INTERVENTION: Daily magnesium supplementation, 532 mg; patient completion of the THI; and daily self-report of TDR. DATA COLLECTION AND ANALYSIS: The main outcome measures were mean TDR scale scores and THI scores as converted to TSS grades. The primary analysis was done on the basis of intention to treat. RESULTS: Twenty-six patients were enrolled; 19 completed the study. The extent of handicap, as measured by THI/TSS, for subjects with slight or greater impairment was significantly decreased (P=.03). Patients who ranked slight or greater on the THI/TSS before intervention showed a significant decrease in the severity of their tinnitus at post-testing (P=.008). CONCLUSION: The results suggest that magnesium may have a beneficial effect on perception of tinnitus-related handicap when scored with the THI.

Trends in Rural Outreach by Orthopedic Surgeons.

BACKGROUND: Sixty million rural residents have limited access to orthopedic care due to a small rural orthopedic surgery workforce. Increases in specialized training add to the challenge of attracting orthopedic surgeons to rural communities. Answering the call for research on models to meet the needs of rural orthopedic patients, we examine long-term trends in visiting consultant clinics (VCCs) in Iowa, a state with a large rural population. METHODS: The Office of Statewide Clinical Education Programs (Carver College of Medicine) compiles an annual report of outreach clinic locations, frequencies and participating physicians. Trends in the total number of VCCs, days and locations (1989-2018) were analysed using joinpoint analysis. RESULTS: Total clinic days grew rapidly from 1992-1997 (Average Percent Change: 19.7%) before a decline ending in 2009 (APC: -4.1%). A new growth period (2009-2013, APC: 7.5%) preceded another decline (APC: -3.6%) ending in 2018. The number of cities hosting a VCC grew from 56 (1989) to a peak of 90 (1999) and fell an average of 0.9% a year thereafter. More than 80% of all VCCs in the last ten years were offered 2 or more times per month. The average participation rate for Iowa-based orthopedic surgeons was 44%. The mean number of VCCs staffed by a single physician was 1.32 (std. dev. = 0.53) with a median of 1. The average number of VCC days per month for a participating physician was 3.22 (std. dev. = 2.41) with a median of 2.66. CONCLUSION: The VCC model of rural outreach is sustainable (30+ year history) and self-funded. Most clinics occur with sufficient frequency to allow timely follow-up care. This model of rural outreach is supported by the participation of a large segment (44%) of Iowa's orthopedic surgeons. Visiting orthopedic surgeons provide access to care in 65 of the 76 Critical Access Hospitals in Iowa offering orthopedic services compared to 8 staffed by a local orthopedic surgeon.Level of Evidence: V.