Understanding gene regulation networks in multicellular organisms is crucial to decipher many complex physiological processes ranging from development to aging. One technique to characterize gene expression with tissue-specificity in whole organisms is single-molecule fluorescence in situ hybridization (smFISH). However, this protocol requires lengthy incubation times, and it is challenging to achieve multiplexed smFISH in a whole organism. Multiplexing techniques can yield transcriptome-level information, but they require sequential probing of different genes. The inefficient macromolecule exchange through diffusion-dominant transport across dense tissues is the major bottleneck. In this work, we address this challenge by developing a microfluidic/electrokinetic hybrid platform to enable multicycle smFISH in an intact model organism, Caenorhabditis elegans. We integrate an ion concentration polarization based ion pump with a microfluidic array to rapidly deliver and remove gene-specific probes and stripping reagents on demand in individual animals. Using our platform, we can achieve rapid smFISH, an order of magnitude faster than traditional smFISH protocols. We also demonstrate the capability to perform multicycle smFISH on the same individual samples, which is impossible to do off-chip. Our method hence provides a powerful tool to study individual-specific, spatially resolvable, and large-scale gene expression in whole organisms.
In order to enhance the reliability of the application to clinical practice of the TLICS classification, we retrospectively reviewed the patients with thoracolumbar spine injuries who underwent magnetic resonance imaging (MRI) and analyzed the validity of the TLICS classification and the necessity of MRI. We enrolled 328 patients with thoracolumbar spine injury who underwent MRI. All patients were classified into conservative and operative treatment groups. The TLICS score of each group was analyzed and the degree of consistent with the recommended treatment through the TLICS classification was examined. Of the total 328 patients, 138 patients were treated conservatively and 190 patients were treated by surgery. Of the 138 patients who underwent conservative treatment, 131 patients (94.9%) had a TLICS score of 4 points or less, and matched with the recommendation score for conservative treatment according to the TLICS classification (match rate 94.9%, 131/138). Of the 190 patients who underwent operative treatment, 160 patients (84.2%) had a TLICS score of 4 points or more (match rate 84.2%, 160/190). All of 30 mismatched patients with a TLICS score of 3 points or less (15.8%) had stable burst fracture without neurological deficit. We retrospectively reviewed the validity of the TLICS classification for the injuries of the thoracolumbar spine, based on MRI in a large group of patients. Treatment with TLICS classification showed high validity, especially in conservative group, and MRI should be an essential diagnostic tool for accurate evaluation of posterior ligamentous complex injury.
by
Michael S. Ramos;
Lucy T. Xu;
Srinidhi Singuri;
Julio C. Castillo Tafur;
Sruthi Arepalli;
Justis P. Ehlers;
Peter K. Kaiser;
Rishi P. Singh;
Aleksandra V. Rachitskaya;
Sunil K. Srivastava;
Jonathan E. Sears;
Andrew P. Schachat;
Amy S. Babiuch;
Sumit Sharma;
Daniel F. Martin;
Careen Y. Lowder;
Arun D. Singh;
Alex Yuan;
Amy S. Nowacki
Purpose: The intravitreal injection (IVI) of pharmacologic agents is the most commonly performed ocular procedure and is associated with a host of complications. Most IVI-related complications data are derived from randomized controlled clinical trials, which report a high adverse event rate. The nature of these protocol-driven trials limit their applicability to the diverse circumstances seen in routine clinical practice. The goal of this study was to determine the prevalence of patient-reported IVI-related complications, their risk factors, and the manner in which patients sought treatment at a tertiary eye care center. Design: Retrospective, institutional review board–approved study. Participants: Forty-four thousand seven hundred thirty-four injections in 5318 unique patients at the Cleveland Clinic Cole Eye Institute from 2012 through 2016. Methods: Intravitreal injection. Main Outcome Measures: Complication occurrence within 15 days of injection. Results: From 2012 through 2016, a total of 44734 injections were performed in 5318 unique patients. Overall, complication rates were low, representing 1.9% of all injections, with 1031 unique complications in 685 patients (12.9%). The most common minor complications, or those not requiring intervention, were irritation (n = 312) and subconjunctival hemorrhage (n = 284). The most common serious complications, or those requiring intervention, were corneal abrasion (n = 46) and iritis (n = 31). Most complications (66%) were managed adequately by a telephone or Epic (Epic Systems Corp., Verona, WI) electronic message encounter only. Importantly, no injection protocol parameter, such as type of anesthesia, preparation, or post-injection medication, increased the risk of a complication. However, a patient's gender, age, number of previous injections, and provider strongly influenced the risk of patient-reported complications. Conclusions: Overall, complication rates seen in routine clinical practice were low compared with clinical trial reporting. Providers should feel confident in the safety and administration of IVI during times when follow-up office visits and resources may be limited. When performing an IVI, factors such as a patient's gender, age, number of previous injections, and provider must be taken into account to ensure the best possible outcomes.
TO THE EDITOR:
Impairment in physical function is an independent predictor of disability, hospitalization, and mortality.1, 2, 3, 4 Geriatric oncology guidelines recommend performing both self-reported [eg, activities of daily living (ADL) and instrumental ADLs (IADL)] and performance-based measures as part of a geriatric assessment.
Introduction: Intertrochanteric hip fractures are a common injury treated by orthopedic surgeons and the incidence rate is rising. Preoperative depression is a known risk factor for postoperative complications in orthopaedic surgery, however its effects on outcomes after geriatric hip fractures is relatively unknown. The purpose of this study was to investigate the relationship between preoperative depression and potential complications following open reduction internal fixation (ORIF) and intramedullary nailing (IMN) of geriatric hip fractures. Methods: In this retrospective study, the Truven Marketscan claims database was used to identify patients over age 65 who underwent ORIF or IMN for a hip fracture from January 2009 to December 2019. Patient characteristics, such as medical comorbidities, were collected and from that 2 cohorts were established (one with and one without depression). Chi-squared and multivariate analysis was performed to investigate the association between preoperative depression and common postoperative complications following intertrochanteric hip fracture surgery. Results: In total, 78,435 patients were identified for analysis. In those patients with preoperative depression, the complications associated with the greatest increased odds after undergoing ORIF were surgical site infections (OR 1.32; CI 1.23-1.44), ED visit for pain (OR 1.27; CI 1.16-1.39), wound complications (OR 1.26; CI 1.14-1.35), and non-union (OR 1.25; CI 1.17-1.33). In the patients with preoperative depression undergoing IMN, the complications associated with the greatest increased odds after were surgical site infections (OR 1.37; CI 1.31- 1.45), ED visit for pain (OR 1.31; CI 1.19-1.44), wound complications (OR 1.23; CI 1.10-1.39), and pneumonia (OR 1.22; CI 1.10-1.31). Conclusions: Preoperative depression in patients undergoing hip fracture surgery is associated with increased complications. Recognizing a patients’ preoperative depression diagnosis can allow physicians to adapt perioperative and postoperative surveillance protocols for these higher risk patients. Further studies are warranted to investigate the degree to which depression is a modifiable risk factor.
Over one million cardiac pacemakers are implanted every year worldwide,[1] of which approximately 200,000 are implanted in the United States alone.[2] Combined with an aging population and increasing pacing indications, these numbers are expected to grow. Since the first pacemaker implantation in 1950s, cardiac pacemaker technology has rapidly advanced. Reduction in generator size, increased battery longevity, quality of pacemaker leads, algorithmic and rate responsive programming―all have revolutionized and transformed the implantation and management of transvenous cardiac pacemaker (TV-PPM).
Acylcarnitines transport fatty acids into mitochondria and are essential for β-oxidation and energy metabolism. Decreased mitochondrial activity results in increased plasma acylcarnitines, and increased acylcarnitines activate proinflammatory signaling and associate with age-related disease. Changes in acylcarnitines associated with healthy aging, however, are not well characterized. In the present study, we examined the associations of plasma acylcarnitines with age (range: 20-90) in 163 healthy, non-diseased individuals from the predictive medicine research cohort (NCT00336570) and tested for gender-specific differences. The results show that long-chain and very long-chain acylcarnitines increased with age, while many odd-chain acylcarnitines decreased with age. Gender-specific differences were observed for several acylcarnitines, e.g., eicosadienoylcarnitine varied with age in males, and hydroxystearoylcarnitine varied in females. Metabolome-wide association study (MWAS) of age-associated acylcarnitines with all untargeted metabolic features showed little overlap between genders. These results show that plasma concentrations of acylcarnitines vary with age and gender in individuals selected for criteria of health. Whether these variations reflect mitochondrial dysfunction with aging, mitochondrial reprogramming in response to chronic environmental exposures, early pre-disease change, or an adaptive response to healthy aging, is unclear. The results highlight a potential utility for untargeted metabolomics research to elucidate gender-specific mechanisms of aging and age-related disease.
During the last 50 years, a tremendous evolution of medical, scientific, and technologic advances has coincided with the successful aging and expansion of the older US population. As a result, the current cardiovascular care of older adults differs vastly from the care of similarly aged patients in prior eras. Our grandparents would scarcely recognize the systems of care and treatment options available today. The use of the computer, internet, and smart phones has skyrocketed in parallel among today's older adults.1 Currently, one in four older adults are smartphone users, but the next wave of older adults will likely all own smartphones. Age‐adjusted heart disease deaths in the United States have declined between 1950 and 2010 with the population living longer and dying less often of acute cardiovascular events.2 These co‐occurring phenomena have brought about dramatic changes in how long we live, how well we live in later years, and even how we die.
The coronavirus disease of 2019 or COVID-19 was first identified in Hubei Province in China in November of 2019 and quickly spread to become a global pandemic. The virus, SARS-Coronavirus-2, is particularly virulent in the elderly who can develop symptoms and become mortally ill within days of contracting the virus. The virus is easily transmitted by droplets (e.g., sneezing and coughing) and communal living settings such as personal care homes can be vulnerable to the spread of the virus. Identifying patients early in the disease process is important to providing appropriate medical interventions. To date, most of the medical literature, including Center for Disease Control guidelines, has relied on three necessary symptoms in making the diagnosis of COVID-19: fever, cough, and shortness of breath. We present four cases of elderly patients who developed altered mental status as their presenting symptom without associated fever or respiratory symptoms.
We have previously shown that aerobic exercise improves measures of verbal fluency in older adults, and such an improvement is correlated with improved cardiovascular reserve (i.e., estimates of VO2). Due to increasing popularity in computer-based cognitive training, we explored whether the addition of cognitive training to aerobic exercise would further enhance the beneficial cognitive impact of exercise. Therefore, this study sought to test the hypothesis that a cognitive training regimen alone would directly improve executive function and that this effect would be potentiated with the addition of aerobic exercise. The interventions lasted 12 weeks, and cognitive assessments were taken immediately prior to and after the interventions. We found that only the groups employing aerobic exercise showed improvements in verbal fluency (semantic and letter) and cardiovascular fitness with no other executive functions being significantly impacted. Cognitive training alone was associated with decreased verbal fluency. These data replicate previous findings which indicate that aerobic exercise may have a remedial or mitigating effect of cognitive decline. In addition, they provide evidence that the addition of concurrent cognitive training to an aerobic exercise program does not provide synergistic improvement in executive functions.