Manganese (Mn), an essential metal and nutrient, is toxic in excess. Toxicity classically results from inhalational exposures in individuals who work in industrial settings. The first known disease ...of inherited Mn excess, identified in 2012, is caused by mutations in the metal exporter SLC30A10 and is characterized by Mn excess, dystonia, cirrhosis, and polycythemia. To investigate the role of SLC30A10 in Mn homeostasis, we first generated whole-body Slc30a10-deficient mice, which developed severe Mn excess and impaired systemic and biliary Mn excretion. Slc30a10 localized to canalicular membranes of hepatocytes, but mice with liver Slc30a10 deficiency developed minimal Mn excess despite impaired biliary Mn excretion. Slc30a10 also localized to the apical membrane of enterocytes, but mice with Slc30a10 deficiency in small intestines developed minimal Mn excess despite impaired Mn export into the lumen of the small intestines. Finally, mice with Slc30a10 deficiency in liver and small intestines developed Mn excess that was less severe than that observed in mice with whole-body Slc30a10 deficiency, suggesting that additional sites of Slc30a10 expression contribute to Mn homeostasis. Overall, these results indicated that Slc30a10 is essential for Mn excretion by hepatocytes and enterocytes and could be an effective target for pharmacological intervention to treat Mn toxicity.
The current paradigm in the field of mammalian iron biology states that body iron levels are determined by dietary iron absorption, not by iron excretion. Iron absorption is a highly regulated ...process influenced by iron levels and other factors. Iron excretion is believed to occur at a basal rate irrespective of iron levels and is associated with processes such as turnover of intestinal epithelium, blood loss, and exfoliation of dead skin. Here we explore iron excretion in a mouse model of iron excess due to inherited transferrin deficiency. Iron excess in this model is attributed to impaired regulation of iron absorption leading to excessive dietary iron uptake. Pharmacological correction of transferrin deficiency not only normalized iron absorption rates and halted progression of iron excess but also reversed body iron excess. Transferrin treatment did not alter the half-life of
Fe in mutant mice.
Fe-based studies indicated that most iron was excreted via the gastrointestinal tract and suggested that iron-loaded mutant mice had increased rates of iron excretion. Direct measurement of urinary iron levels agreed with
Fe-based predictions that urinary iron levels were increased in untreated mutant mice. Fecal ferritin levels were also increased in mutant mice relative to wild-type mice. Overall, these data suggest that mice have a significant capacity for iron excretion. We propose that further investigation into iron excretion is warranted in this and other models of perturbed iron homeostasis, as pharmacological targeting of iron excretion may represent a novel means of treatment for diseases of iron excess.
The purpose of this study is to analyze the Instagram practices of current orthopaedic surgeons and the components associated with highest reach and interactions.
The top 25 orthopaedic surgeon ...Instagram profiles using the hashtag #ortho were ranked by the number of followers. Account information regarding followers, posts, engagement percentage, average likes, average comments, average video view, average video likes, average video comments, and estimated cost per post was recorded using social media marketing tools. An analysis of each Instagram profiles’ top 10 posts, based on number of likes, was conducted. A coding framework was developed to categorized posting strategies utilized.
Twenty-five Instagram accounts and 250 Instagram posts were included in the analysis. Accounts with increased engagement rating had a significantly greater number of likes and video views. When examining post characteristics that influenced the number of likes a post generated, posts that elicited negative emotions received 52.6% and 70.7% more likes than positive emotions (P = .04) and neutral emotions (P < .01), respectively. Upon assessment of posting characteristics that influenced the number of comments a post generated, promotional posts were shown to have 43.7% fewer comments than nonpromotional posts (P = .02). When evaluating factors that influenced total number of interactions a post generated, it was found that posts that asked questions generated 26.4% more interactions (P < .01) than those that do not.
The present investigation found that the most effective strategies to generate more interactions on Instagram are those that elicit emotional responses and provoke viewer engagement by asking questions and directing actions. Additionally, it was found that promotional content was not well received by viewers.
Orthopaedic surgeons have an opportunity to connect with colleagues, patients, and interested viewers through social media platforms in order to enhance their practice, disseminate educational content, and contribute to the social media presence of orthopaedic surgery.
Tangles are deposits of hyperphosphorylated tau, which are found in multiple neurodegenerative disorders that are referred to as tauopathies, of which Alzheimer's disease (AD) is the most common. ...Tauopathies are clinically characterized by dementia and share common cortical lesions composed of aggregates of the protein tau.
In this study, we explored the therapeutic potential of tolfenamic acid (TA), in modifying disease processes in a transgenic animal model that carries the human tau gene (hTau).
Behavioral tests, Western blotting and Immunohistochemical analysis were used to demonstrate the efficacy of TA.
Treatment of TA improved improving spatial learning deficits and memory impairments in young and aged hTau mice. Western blot analysis of the hTau protein revealed reductions in total tau as well as in sitespecific hyperphosphorylation of tau in response to TA administration. Immunohistochemical analysis for phosphorylated tau protein revealed reduced staining in the frontal cortex, hippocampus, and striatum in animals treated with TA.
TA holds the potential as a disease-modifying agent for the treatment of tauopathies including AD.
To investigate the demographic factors that influence time to respond (TTR), time to completion (TTC), and response rate when using a text messaging-based system and to determine the feasibility and ...applicability of mobile messaging-based services for collection of patient-reported outcomes among orthopaedic sports medicine patients.
On the day of surgery, patient mobile phone number was collected and the automated mobile messaging service (MOSIO, Seattle, WA) messaged patients for 10 ``days postoperatively. Patient visual analog scale (VAS) scores were collected 3 times daily, side effects were asked each evening, and Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference (PI) Short Form was collected on postoperative day 3 and 7.
A total of 177 patients were enrolled in the study. The overall response rate to the survey questions was 75.0%. For all patients, the average TTR of questions was 35.09 ± 12.57 minutes. The TTC was 2.75 ± 3.56 minutes for PROMIS-PI, 3.51 ± 1.26 minutes for VAS, and 3.80 ± 6.87 for side-effect questions. When patients were stratified into age groups, the youngest group, 16 to 32 years, had the greatest response rate of 85.2% and patients in the 49 to 59 years group had the lowest response rate of 68.4% and 69.1%, respectively (P < .001). There was no significant difference in the TTR or TTC for VAS, PROMIS-PI, or side-effect questions when patients were stratified by age or sex groups (P > .05).
Collectively, all age groups successfully achieved a mean response rate of 75%; however, significantly lower response rates were observed for patients >49 years old. Differences in age and sex did not impact the overall TTR or TTC for VAS, PROMIS-PI, or side-effect questions. Mobile-based applications present as an emerging opportunity to track postoperative outcome scores and reduce clinic survey load.
Case series, level of evidence IV.
High dose manganese (Mn) exposure can result in changes in tissue concentrations of other essential metals due to Mn-induced alterations in metal absorption and competition for metal transporters and ...regulatory proteins. We evaluated responses in mice with a Parkin gene defect (parkin mice) and a wildtype strain (C57BL/6J) following neonatal Mn exposure. Neonatal parkin and C57BL/6J littermates were randomly assigned to 0, 11, or 25mg Mn/kg-day dose groups with oral exposures occurring from postnatal day (PND) 1 through PND 28. We report liver, femur, olfactory bulb, striatum, and frontal cortex iron, copper, and zinc concentrations and changes in hepatic gene expression of different metal transporters in PND 29 parkin and C57BL/6J mice. A companion manuscript (Foster et al., 2017) 1 describes the primary study findings. This data provides insights into strain differences in the way Mn interacts with other trace metals in mice.
Anxiety and depression are among the most common mental health disorders in the United States and have been linked to increased health-care utilization and poorer clinical outcomes. However, data on ...the relationship between anxiety and depression and outcomes after shoulder arthroplasty (SA) are both limited and conflicting.
This retrospective cohort study examined the influence of a preoperative diagnosis of anxiety and/or major depressive disorder (MDD) on outcomes following shoulder arthroplasty, such as range of motion, pain, perioperative and postoperative complications, and readmission rates. A retrospective chart review of our health system’s electronic medical record was performed for dates of service January 2014–December 2019. Patients who underwent primary total shoulder arthroplasty or reverse total shoulder arthroplasty were considered for inclusion. These patients were then divided into two groups based on the presence or absence of an anxiety disorder and/or MDD in their past medical history.
595 patients with a minimum follow-up of one year were considered for analysis. Of these, 205 patients (34.5%) had diagnoses of an anxiety and/or MDD and were assigned to the psychiatric comorbidity group, while 390 (65.5%) were assigned to the control group. The psychiatric comorbidity group was significantly younger (68.3 ± 9.3 vs. 70.5 ± 10.0, P = .008) and more heavily female (68.7% vs. 48.7%, P < .001). The length of stay was significantly longer in the psychiatric comorbidity group than in the control group (1.9 ± 2.4 vs. 1.5 ± 0.9 days, P = .023). Postoperative range of motion, visual analog scale pain scores (1.8 ± 2.7 vs. 1.3 ± 2.3, P = .059), complication rates (7.8% vs. 6.9%, P = .681), and revision rates (4.9% vs. 3.6%, P = .448) were not significantly different between the psychiatric comorbidity and control groups, respectively. All-cause emergency department visitation and hospital readmission rates were also similar between the two groups at 30, 60, and 90 days postoperatively.
Our results suggest that a preoperative diagnosis of MDD or anxiety does not affect pain, postoperative outcomes, complications, or readmission rates following shoulder arthroplasty.
Published Lyme meningitis treatment studies are limited by outcome measures that cannot capture day-to-day differences in clinical improvement. Our goal was to use expert consensus to develop a daily ...measurement instrument for assessing clinical improvement in children with Lyme meningitis. We assembled a panel of 24 nationally recognized Lyme disease experts to develop a pediatric daily symptom measurement instrument. Experts responded to four rounds of surveys, receiving feedback about the previous round prior to each subsequent round with anonymity for participants and responses. Using modified Delphi methods, we established a novel Lyme meningitis outcome instrument. The final Pediatric Lyme Meningitis Symptom Measurement instrument includes five items: headache (Likert scale), neck pain/stiffness (Likert scale), fever (yes/no), light sensitivity (yes/no) and vision problems (yes/no). We defined three consecutive days with a symptom score of zero as the minimum to define clinical improvement. Using expert consensus, we developed a novel Pediatric Lyme Meningitis Symptom Measurement instrument to measure treatment response daily for children with Lyme meningitis enrolled in clinical studies.
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