Intranasal Administration of Sugarcane Ash Causes Chronic Kidney Disease in Rats.

Background. Silica nanoparticles found in sugarcane ash have been postulated to be a toxicant contributing to chronic kidney disease of unknown etiology (CKDu). However, while the administration of manufactured silica nanoparticles is known to cause chronic tubulointerstitial disease in rats, the effect of administering sugarcane ash on kidney pathology remains unknown. Here we investigate whether sugarcane ash can induce CKD in rats. Methods. Sugarcane ash was administered for 13 weeks into the nares of rats (5 mg/day for 5d/week), and blood, urine and kidney tissues were collected at 13 weeks (at the end of ash administration) and in a separate group of rats at 24 weeks (11 weeks after stopping ash administration). Kidney histology was evaluated, and inflammation and fibrosis (collagen deposition) measured. Results. Sugarcane ash exposure led to the accumulation of silica in the kidneys, lungs, liver and spleen of rats. Mild proteinuria developed although renal function was largely maintained. However, biopsies showed focal glomeruli with segmental glomerulosclerosis, and tubulointerstitial inflammation and fibrosis that tended to worsen even after the ash administration had been stopped. Staining for the lysosomal marker, LAMP-1, showed decreased staining in ash administered rats consistent with lysosomal activation. Conclusion. Sugarcane ash containing silica nanoparticles can cause CKD in rats.

Exacerbation of Renal, Cardiovascular, and Respiratory Outcomes Associated with Changes in Climate.

Exposure to environmental variables including declining air quality and increasing temperatures can exert detrimental effects on human health including acute exacerbations of chronic diseases. We aim to investigate the association between these exposures and acute health outcomes in a rural community in Colorado. Meteorological and adult emergency department visit data were retrospectively collected (2013-2017); for asthma outcomes, additional data were available (2003-2017). Daily environmental exposure data included PM10, maximum daily temperature (MDT), and mean humidity and precipitation. Total daily counts of emergency department (ED) diagnoses for myocardial infarction, congestive heart failure, urolithiasis, and exacerbation of chronic obstructive pulmonary disease (COPD) and asthma, were calculated during the study period. Time series models using generalized estimating equations were fit for each disease and included all four environmental factors. Between 2013 and 2017, asthma and COPD exacerbation accounted for 30.8% and 25.4% of all ED visits (n=5,113), respectively. We found that for every 5˚C increase in MDT, the rate of urolithiasis visits increased by 13% (95% CI: 2%, 26%) and for every 10µg/m3 increase in 3-day moving average PM10, the rate of urolithiasis visits increased by 7% (95% CI: 1%, 13%). The magnitude of association between 3-day moving average PM10 and rate of urolithiasis visits increased with increasing MDT. The rate of asthma exacerbation significantly increased as 3-day, 7-day, and 21-day moving average PM10 increased. This retrospective study on ED visits is one of the first to investigate the impact of several environmental exposures on adverse health outcomes in a rural community. Research into mitigating the negative impacts of these environmental exposures on health outcomes is needed.

Inhaled silica nanoparticles cause chronic kidney disease in rats.

Silica nanoparticles (SiNPs) released during the burning of sugarcane have been postulated to have a role in chronic kidney disease of unknown etiology. We tested the hypothesis that pristine SiNPs of the size present in sugarcane might cause chronic kidney injury when administered through the lung in rats. We administered 200- or 300-nm amorphous SiNPs twice weekly (4 mg/dose), or vehicle by oropharyngeal aspiration for 13 wk to rats followed by euthanasia after an additional 13 wk (26 wk total). Tissues were evaluated for the presence of SiNPs and evidence of histological injury. Both sizes of SiNPs caused kidney damage, with early tubular injury and inflammation (at week 13) that continued to inflammation and chronic fibrosis at week 26 despite discontinuation of the SiNP administration. Both sizes of SiNPs caused local inflammation in the lung and kidney and were detected in the serum and urine at week 13, and the 200-nm particles were also localized to the kidney with no evidence of retention of the 300-nm particles. At week 26, there was some clearance of the 200-nm silica from the kidneys, and urinary levels of SiNPs were reduced but still significant in both 200- and 300 nm-exposed rats. In conclusion, inhaled SiNPs cause chronic kidney injury that progresses despite stopping the SiNP administration. These findings support the hypothesis that human exposure to amorphous silica nanoparticles found in burned sugarcane fields could have a participatory role in chronic kidney disease of unknown etiology.NEW & NOTEWORTHY Inhalation of silica nanoparticles (SiNPs) released during the burning of sugarcane has been postulated to have a role in chronic kidney disease of unknown etiology (CKDu). We administered 200- and 300-nm amorphous SiNPs to rats by aspiration and observed kidney damage with tubular injury and inflammation that persisted even after stopping the SiNP exposure. These findings support the hypothesis that human exposure to SiNPs found in sugarcane ash could have a participatory role CKDu.

Urine tungsten and chronic kidney disease in rural Colorado.

BACKGROUND: Chronic kidney disease (CKD) is a cause of global morbidity and mortality in agricultural communities. The San Luis Valley (SLV) is a rural agricultural community in southern Colorado with geographic and sociodemographic risk factors for CKD, including a water supply contaminated by heavy metals. METHODS: We obtained pre-existing sociodemographic, clinical, and urine trace metal data for 1659 subjects from the San Luis Valley Diabetes Study, a prospective cohort study. We assessed prospective associations between urine tungsten (W) and time-to-CKD using accelerated failure time models (n = 1659). Additionally, logistic models were used to assess relationships between urine W and renal injury markers (NGAL, KIM1) using Tobit regression (n = 816), as well as epidemiologically-defined CKD of unknown origin (CKDu) using multiple logistic regression (n = 620). RESULTS: Elevated urine W was strongly associated with decreased time-to-CKD, even after controlling for hypertension and diabetes. Depending on how CKD was defined, a doubling of urine W was associated with a 27% (95% CI 11%, 46%) to 31% (14%, 51%) higher odds of developing CKD within 5 years. The relationship between urine W and select renal injury markers was not significant, although urine NGAL was modified by diabetes status. Elevated (>95%ile) urinary W was significantly associated with CKDu (OR 5.93, 1.83, 19.21) while adjusting for known CKD risk factors. CONCLUSIONS: Our data suggest that increased exposure to W is associated with decreased time-to-CKD and may be associated with CKDu. Given persistence of associations after controlling for diabetes and hypertension, W may exert a primary effect on the kidney, although this needs to be evaluated further in future studies.

Acute Illness Associated With Cannabis Use, by Route of Exposure: An Observational Study.

Background: Little is known about the relative harms of edible and inhalable cannabis products. Objective: To describe and compare adult emergency department (ED) visits related to edible and inhaled cannabis exposure. Design: Chart review of ED visits between 1 January 2012 and 31 December 2016. Setting: A large urban academic hospital in Colorado. Participants: Adults with ED visits with a cannabis-related International Classification of Diseases, Ninth or 10th Revision, Clinical Modification (ICD-9-CM or ICD-10-CM), code. Measurements: Patient demographic characteristics, route of exposure, dose, symptoms, length of stay, disposition, discharge diagnoses, and attribution of visit to cannabis. Results: There were 9973 visits with an ICD-9-CM or ICD-10-CM code for cannabis use. Of these, 2567 (25.7%) visits were at least partially attributable to cannabis, and 238 of those (9.3%) were related to edible cannabis. Visits attributable to inhaled cannabis were more likely to be for cannabinoid hyperemesis syndrome (18.0% vs. 8.4%), and visits attributable to edible cannabis were more likely to be due to acute psychiatric symptoms (18.0% vs. 10.9%), intoxication (48% vs. 28%), and cardiovascular symptoms (8.0% vs. 3.1%). Edible products accounted for 10.7% of cannabis-attributable visits between 2014 and 2016 but represented only 0.32% of total cannabis sales in Colorado (in kilograms of tetrahydrocannabinol) during that period. Limitation: Retrospective study design, single academic center, self-reported exposure data, and limited availability of dose data. Conclusion: Visits attributable to inhaled cannabis are more frequent than those attributable to edible cannabis, although the latter is associated with more acute psychiatric visits and more ED visits than expected. Primary Funding Source: Colorado Department of Public Health and Environment.

Drugs of Abuse and Novel Psychoactive Substances at Outdoor Music Festivals in Colorado.

BACKGROUND: Drugs of abuse (DOA) are widely used in the United States and are ubiquitous at outdoor music festivals. Attendees at music festivals are at high-risk for novel psychoactive substance (NPS) use, which is becoming more prevalent worldwide. No U.S. studies have employed an qualitative approach to investigate the etiologies of both traditional DOA and NPS use amongst music festival attendees. OBJECTIVES: The objective of this study was to improve understanding of the knowledge, attitudes, beliefs, and practices of festival attendees using NPS and DOA. METHODS: We conducted semi-structured interviews of 171 attendees during the Sonic Bloom and Arise music festivals in Colorado in 2015 and 2016. Discrete variables were summarized with descriptive statistics. The anonymous, multi-domain interview documented the knowledge, attitudes beliefs, and practices underlying DOA use, which were analyzed with qualitative methods. RESULTS: We enrolled 171 participants that endorsed DOA use at the festivals. Most were experienced DOA users, who perceived minimal risks associated with DOA and NPS use. Nearly all unanimously reported normalization of DOA at music festivals. Participants popularly cited empathogenic, entactogenic, and entheogenic effects of DOA as their primary motivations for use. NPS use was endorsed by 39.8% (n = 68) of respondents, all of whom identified as being experienced DOA users. CONCLUSIONS: This population of novel psychoactive substance users is primarily composed of experienced drug users that endorsed use because of low cost, minimal perceived risk, accessibility, and normalization of drug use at music festivals.

Identifying when choice helps: clarifying the relationships between choice making, self-construal, and pain.

Prior research indicates that making choices before a painful task can sometimes reduce pain. We examined the possibility that independent and interdependent self-construals moderate the effect of choice on pain. Further, we tested between two types of choice: instrumental and non-instrumental. Healthy normotensive undergraduates were randomly assigned to one of three conditions prior to the cold pressor task. Participants in an instrumental choice condition selected which hand to immerse in the water and were told this choice might help reduce their pain. Non-instrumental choice participants selected which hand to immerse but were given no information about potential pain reduction. Control participants were given no choice or additional instructions. Low interdependence individuals reported less pain than high interdependence individuals-but only when given an instrumental choice. These data indicate that not all forms of choice reduce pain and not all individuals benefit from choice. Instead, individuals low in interdependence exhibit pain relief from instrumental choices.

The growth rate of multicolor Ramsey numbers of 3-graphs.

The q-color Ramsey number of a k-uniform hypergraph G,  denoted r(G; q), is the minimum integer N such that any coloring of the edges of the complete k-uniform hypergraph on N vertices contains a monochromatic copy of G. The study of these numbers is one of the most central topics in combinatorics. One natural question, which for triangles goes back to the work of Schur in 1916, is to determine the behavior of r(G; q) for fixed G and q tending to infinity. In this paper, we study this problem for 3-uniform hypergraphs and determine the tower height of r(G; q) as a function of q. More precisely, given a hypergraph G, we determine when r(G; q) behaves polynomially, exponentially or double exponentially in q. This answers a question of Axenovich, Gyárfás, Liu and Mubayi.

Locating the sural nerve during calcaneal (Achilles) tendon repair with confidence: a cadaveric study with clinical applications.

The sural nerve is at risk of iatrogenic injury even during minimally invasive operative procedures to repair the calcaneal (Achilles) tendon. Through 107 cadaveric leg dissections, the data derived from the present study was used to develop a regression equation that will enable surgeons to estimate the intersection point at which the sural nerve crosses the lateral border of the Achilles tendon, an important surgical landmark. In most cases, the sural nerve crossed the lateral border of the Achilles tendon 8 to 10 cm proximal to the superior border of the calcaneal tuberosity. By simply measuring the leg length of the patient (from the base of the heel to the flexor crease of the popliteal fossa), surgeons can approximate the location of this intersection point with an interval length of 0.68 to 1.80 cm, with 90% confidence, or 0.82 to 2.15 cm, with 95% confidence. For example, for a patient with a lower leg length of 47.0 cm, the mean measurement in the present study, a surgeon can be 90% confident that the sural nerve will cross the lateral border of the Achilles tendon 8.28 to 8.96 cm (interval width of 0.68 cm) proximal to the calcaneal tuberosity. Currently, ultrasound and clinical techniques have been implemented to approximate the location of the sural nerve. The results of the present study offer surgeons another method, that is less intensive, to locate reliably and subsequently avoid damage to the sural nerve during calcaneal (Achilles) tendon repair and other procedures of the posterolateral leg and ankle.

Clinical implications of novel variants of the fibularis (peroneus) quartus muscle inserting onto the cuboid bone: peroneocuboideus and peroneocalcaneocuboideus.

Two variants of the fibularis (peroneus) quartus muscle were identified and photographed in the legs of a 70-year-old white male cadaver. A rare peroneocuboideus (fibulocuboideus) muscle (as described by Chudzinski) and a novel peroneocalcaneocuboideus (fibulocalcaneocuboideus) muscle was found in the right and left leg, respectively. The latter muscle has not been previously reported and was termed "peroneocalcaneocuboideus" on the basis of its origin and insertions. Also, the distal attachment of both muscles inserted onto the distal lip of the peroneal sulcus of the cuboid bone, which differs from the historical data. The insertion of the peroneocuboideus muscle was previously described as being at the tuberosity of the cuboid bone or, simply, the lateral surface of the cuboid. Therefore, the present case study provides the first gross anatomic photographs of these variant leg muscles along their entire length, identifies a novel fibularis quartus variant, and describes a new insertion site for the peroneocuboideus muscle. Throughout our report, the historical data are reviewed to list the prevalence and describe the clinical implications of the fibularis quartus muscle and its variants. The presence of variant fibularis quartus muscles has been known to cause lateral ankle pain and stenosis, ankle instability, fibular tenosynovitis, subluxation of the fibular (peroneal) tendons, and longitudinal splitting of the fibularis brevis tendon in radiologic and case studies. Therefore, surgeons, radiologists, and clinicians should be aware of these variant muscles when considering various diagnoses, interpreting radiographs, and pursuing surgical intervention to relieve lateral ankle pathologic features.

The fibulocalcaneus (peroneocalcaneus) internus muscle of MacAlister: Clinical and surgical implications.

A fibulocalcaneus (peroneocalcaneus) internus (PCI) muscle (of MacAlister) was identified and photographed in the left leg of a 78-year-old Caucasian female cadaver. This case study provides the first gross anatomical photo of this anomalous leg muscle and represents the first gross anatomical dissection of this muscle since 1914. The PCI muscle arose from the distal third of the fibula, posterior intermuscular septum of the leg, and flexor hallucis longus muscle. The PCI muscle inserted into the inferior surface of the medial calcaneus distal to the coronoid fossa, a small depression between the anterior tuberosity and the anterior apex of the sustentaculum tali. This insertion point differs from the historical literature, which commonly refers to the muscle inserting into the inferior surface of the sustentaculum tali of the calcaneus or simply distal to the sustentaculum tali into the medial aspect of the calcaneus. The PCI muscle is one of the least common muscular variants associated with the ankle joint, and it has been implicated in posterior ankle pain and impingement, as well as involvement in tarsal tunnel syndrome. This muscle is often confused with the flexor digitorum accessorius longus (FDAL) muscle. Additionally, this study describes ways to differentiate between the PCI and FDAL muscles in the lower leg. Radiologists and clinicians should be aware of this anomalous muscle when considering various diagnoses, interpreting radiographs, and pursuing surgical intervention to relieve posterior ankle symptoms.

COVID-19 and Public Policy Imperatives: A Trainee Call to Action.

The COVID-19 pandemic has exacerbated the flaws in the U.S. employer-based health insurance system, magnified racial disparities in health and health care, and overwhelmed the country's underfunded public health infrastructure. These are the same systematic failures that have always harmed and killed the nation's most vulnerable. While everyone wishes for an end to this national tragedy, the authors believe a new normal must be defined for the postpandemic period.In the postpandemic period, policies that were once labeled radical and impossible will be urgent and necessary. Examples of such policies include providing universal health care, dismantling the structures that propagate racism and injustice, and reinvesting in public health. Previous research by the authors has shown that their medical student colleagues recognize that it is their responsibility to address policies that harm patients and to support reforms at the scale the authors propose. This commitment to a better future is reflected in the widespread mobilization of medical students seen across the United States. Recognizing that the old normal is unsustainable, the authors call on those who previously benefited from the status quo to instead seek a new postpandemic normal that works for all.

Today's Students, Tomorrow's Physicians: Opinions on Enacted and Prospective Health Care Policies.

Future physicians will be key stakeholders in the formation, implementation, and success of health care policies enacted during their careers, though little is known of their opinions of enacted and proposed policies since the 2016 U.S. presidential election. This study aimed to understand the opinions of medical students related to policies including, but not limited to, protections for people with pre-existing conditions, a public option on the private exchange, and single-payer health care. Online surveys were completed by 1,660 medical students at 7 U.S. medical schools between October 2017 and November 2017. The authors used multiple logistic regression to examine associations between student characteristics and support of policies. In total, 1,660 of 4,503 (36.9%) eligible medical students completed the survey. A majority of respondents identified 4 extant Affordable Care Act policies as important, including its protections for patients with pre-existing conditions (95.3%) and Medicaid expansion (77.8%). With respect to prospective reforms, 82.6% supported a public insurance option, and 70.5% supported a single-payer health care system. Only 2.2% supported reducing funding for Medicaid. Although views varied by sex, anticipated specialty, and political affiliation, medical students largely supported prospective policies that would expand insurance coverage and access to health care.

Looking to the Future: Medical Students' Views on Health Care Reform and Professional Responsibility.

PURPOSE: Although medical students will influence the future U.S. health care system, their opinions on the Patient Protection and Affordable Care Act (ACA) have not been assessed since the 2016 presidential election and elimination of key ACA provisions. Understanding medical students' views on health care policy and professional obligations can provide insight into issues that will be shaped by the next generation of physicians. METHOD: From October 2017 to November 2017, the authors conducted an electronic survey of medical students from seven U.S. institutions to elicit opinions regarding the ACA and their professional responsibility to address health policy. Participant demographics and responses were tabulated, and multiple logistic regression models were used to assess the associations of demographic characteristics with student opinions. RESULTS: Completed surveys were returned by 1,660/4,503 (36.9%) eligible medical students. Respondent demographics were similar to national estimates. In total, 89.1% (1,475/1,660) supported the ACA, and 82.0% (1,362/1,660) reported that they understood the health care law. Knowledge of the law's provisions was positively associated with support for the ACA (P < .001). Most students (85.8%; 1,423/1,660) reported addressing health policy to be a professional responsibility. Political affiliation was consistently associated with student opinions. CONCLUSIONS: Most medical students support the ACA, with greater levels of support among medical students who demonstrated higher levels of objective knowledge about the law. Furthermore, students indicated a professional responsibility to engage in health policy, suggesting that tomorrow's physicians are likely to participate in future health care reform efforts.

Morphological Spectra of Adult Human Stellate Ganglia: Implications for Thoracic Sympathetic Denervation.

Cardiac sympathetic denervation (CSD) to treat ventricular arrhythmias (VAs) requires transection at the middle or lower third of stellate (cervicothoracic) ganglia (SG). However, the morphological appearance of the adult SG and distribution of neuronal somata within it are not well described. To determine the morphology of left and right SG (LSG and RSG) and the distribution of somata within. LSG and RSG (n = 28) from 14 embalmed adult cadavers were dissected intact. Weight, volume, height, morphologic appearance, relationship between C8 and T1 ganglia (which form the SG) were determined, along with histology. Demographics, history of cardiac disease, and cause of death were also reviewed. Mean age of the subjects was 76 ± 13 years, and 5/14 were male. Three distinct morphologies of SG were identified: fusiform-rounded; fusiform-elongated; and bilobed. RSG and LSG did not differ in weight or volume. RSG were longer than LSG (2.05 ± 0.28 cm vs. 1.66 ± 0.47 cm, P = 0.024). Bilobed morphology was most common in RSGs (8/14), while fused, elongated was most common in LSG (8/14). RSGs lacked fused, rounded appearance, while 28.6% of LSG appeared as such. Histologically, one focus of somata was seen in fused rounded ganglia, while fused elongated SG had somata distributed throughout. Bilobed SG demonstrated two foci of somata, with the interconnecting stalk containing sparse somata. SG appears in three major forms and contains varying distributions of somata. Larger studies are warranted to define the relationship between gross anatomy and distribution of neuronal somata to improve the efficacy of CSD in treating VAs. Anat Rec, 301:1244-1250, 2018. © 2018 Wiley Periodicals, Inc.

Mental Health-related Emergency Department Visits Associated With Cannabis in Colorado.

BACKGROUND: Cannabis legalization in Colorado resulted in increased cannabis-associated health care utilization. Our objective was to examine cooccurrence of cannabis and mental health diagnostic coding in Colorado emergency department (ED) discharges and replicate the study in a subpopulation of ED visits where cannabis involvement and psychiatric diagnosis were confirmed through medical review. METHODS: We collected statewide ED International Classification of Diseases, 9th Revision, Clinical Modification diagnoses from the Colorado Hospital Association and a subpopulation of ED visits from a large, academic hospital from 2012 to 2014. Diagnosis codes identified visits associated with mental health and cannabis. Codes for mental health conditions and cannabis were confirmed by manual records review in the academic hospital subpopulation. Prevalence ratios (PRs) of mental health ED discharges were calculated to compare cannabis-associated visits to those without cannabis. Rates of mental health and cannabis-associated ED discharges were examined over time. RESULTS: Statewide data demonstrated a fivefold higher prevalence of mental health diagnoses in cannabis-associated ED visits (PR = 5.35, 95% confidence interval [CI], 5.27-5.43) compared to visits without cannabis. The hospital subpopulation supported this finding with a fourfold higher prevalence of psychiatric complaints in cannabis attributable ED visits (PR = 4.87, 95% CI = 4.36-5.44) compared to visits not attributable to cannabis. Statewide rates of ED visits associated with both cannabis and mental health significantly increased from 2012 to 2014 from 224.5 to 268.4 per 100,000 (p < 0.0001). CONCLUSIONS: In Colorado, the prevalence of mental health conditions in ED visits with cannabis-associated diagnostic codes is higher than in those without cannabis. There is a need for further research determining if these findings are truly attributed to cannabis or merely coincident with concurrent increased use and availability.