Bulletin of Computer Science and Electrical Engineering (BCSEE)
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Association Between Fecal Contamination and Outcomes After Emergent General Surgery Colorectal Resection: A Post Hoc Analysis of an Eastern Association for the Surgery of Trauma (EAST) Multicenter Study
No full textStructure of mitoribosome reveals mechanism of mRNA binding, tRNA interactions with L1 stalk, roles of cofactors and rRNA modifications
No full textThe mitoribosome translates mitochondrial mRNAs and regulates energy conversion that is a signature of aerobic life forms. We present a 2.2 Å resolution structure of human mitoribosome together with validated mitoribosomal RNA (rRNA) modifications, including aminoacylated CP-tRNA
Val
. The structure shows how mitoribosomal proteins stabilise binding of mRNA and tRNA helping to align it in the decoding center, whereas the GDP-bound mS29 stabilizes intersubunit communication. Comparison between different states, with respect to tRNA position, allowed to characterize a non-canonical L1 stalk, and molecular dynamics simulations revealed how it facilitates tRNA transition in a way that does not require interactions with rRNA. We also report functionally important polyamines that are depleted when cells are subjected to an antibiotic treatment. The structural, biochemical, and computational data illuminate the principal functional components of the translation mechanism in mitochondria and provide the most complete description so far of the structure and function of the human mitoribosome
Endometrioid Squamous Proliferations of the Endometrium Express Alpha-Methylacyl-CoA Racemase (P504s)
No full textSquamous morular metaplasia is closely associated with endometrioid proliferative lesions, such as endometrial intraepithelial neoplasia, whereas endometrioid adenocarcinomas (endometrioid carcinoma) may also demonstrate squamous differentiation (morular or nonmorular). Alpha-methylacyl-CoA racemase (AMACR; P504s) is an immunohistochemistry marker expressed in many tumors, including prostate adenocarcinoma, renal cell carcinoma, and a subset of gynecologic tumors, predominantly of clear cell histology. In small biopsy samples, the distinction between cervical high-grade squamous intraepithelial lesions (HSILs) involving endocervical glands from endometrioid squamous proliferation can be challenging, given the anatomic vicinity and some degree of morphologic overlap. Following the observation of AMACR positivity by immunohistochemistry within squamous morules in an index case, 35 endometrial samples containing squamous morular metaplasia (25) and nonmorular squamous metaplasia (10), and 32 cases of cervical HSIL involving endocervical glands were stained with AMACR. The endometrial cohort consisted of 2 benign anovulatory endometrium, 7 endometrial polyps, 7 endometrial intraepithelial neoplasia, 4 atypical polypoid adenomyomas, and 15 endometrioid adenocarcinomas (endometrioid carcinoma). Positive cases were scored as diffuse (≥50%) or focal (<50%). AMACR staining was present in 96.7% of endometrial squamous lesions, including 14 (93.3%) of endometrioid carcinomas, and in all cases of endometrial intraepithelial neoplasia, endometrial polyps, atypical polypoid adenomyomas, and anovulatory endometrium with squamous morular metaplasia or nonmorular squamous metaplasia. In comparison, only 2 cases (5.8%) of cervical HSIL demonstrated positivity with AMACR. In conclusion, AMACR can reliably differentiate the cervical versus endometrial origin of squamous lesions in small biopsy specimens
647-P: Patient Preferences Informing Choice of Second-Line Type 2 Diabetes Medications
No full textAvailable second-line glucose-lowering medications for type 2 diabetes (T2D) have variable efficacy and side effect profiles, administration requirements, and impacts on short-term and long-term health outcomes. Therefore, medication choice is informed by each patient's clinical needs and personal preferences. However, patient rationale for selecting a second-line medication for T2D is not well understood. In this mixed methods study, 40 adults with T2D across 2 health systems in the U.S. completed an individual ranking activity, sorting 16 health outcomes and 8 medication attributes by relative importance and providing context on ranking decisions. Participants were between 45-64 years old (38%), non-Hispanic White (50%) or Black (38%), 15% Hispanic, and 55% women. For health outcomes, the highest proportion of patients ranked blindness (63%), death (60%), heart attack (48%), or heart failure (48%) as very important. For medication attributes, most participants indicated that greater efficacy with respect to lowering hemoglobin A1c was very important (68%), followed by oral administration (45%) and absence of gastrointestinal side effects (38%). Combinations of outcomes and attributes ranked as very important were highly heterogeneous across individual participants, with only 2/40 patients ranking the same combination. Qualitative findings indicated that outcome importance is a function of perceived severity, susceptibility, personal relevance, preventability, and potential life impacts. For medication attributes, most participants emphasized the primary importance of lowering blood glucose and hemoglobin A1c, while treatment processes and side effects were secondary and largely idiosyncratic to the patient's lifestyle, prior experiences, and preferences. Findings underscore the importance of engaging patients in conversations about goals and preferences for care and contextualizing therapeutic decisions in patient-described priorities for T2D management. Disclosure E.Golembiewski: None. A.E.Garcia: None. E.Polley: None. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter. R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. J.Brito: None. V.M.Montori: None. M.Mickelson: None. R.G.Mccoy: Consultant; Emmi. Funding Patient-Centered Outcomes Research Institute (DB-2020C2-20306
Hurricane Vulnerability and Constrained Choices among Mobile Home Park Residents in South Florida
No full textSix Myths of the Anterior Segment: Misunderstandings and Critical Thinking in Ophthalmology
No full textMeasuring Ambulatory Racial and Ethnic Neurologic Disparities With the Axon Registry
No full textThe primary objective is to examine potential racial and ethnic (R/E) disparities in ambulatory neurology quality measures within the American Academy of Neurology Axon Registry. R/E disparities in neurologic US morbidity and mortality have been clearly documented. Despite these findings, there have been no nationwide examinations of how ambulatory neurologic care affects these negative health outcomes.
This was a retrospective nonrandomized cohort study of patients in the AAN Axon Registry. The Axon Registry is a neurology-specific outpatient quality registry that collects, reports, and analyzes real-world deidentified electronic health record (EHR) data. Patients were included in the study if they contributed toward one of the selected quality measures for multiple sclerosis, epilepsy, Parkinson disease, or headache during the study period of January 1, 2019-December 31, 2019. Descriptive analyses of patient demographics were performed and then stratified by race and ethnicity.
There were a total of 633,672 patients included in these analyses. Separate analyses were performed for race (64% White, 8% Black, 1% Asian, and 27% unknown) and ethnicity (52% not Hispanic, 5% Hispanic, and 43% unknown). The mean age ranged from 18 to 55 years, with 61% female and 39% male. Quality measures were chosen based on completeness of R/E data and were either process or outcomes focused. Statistically significant differences were noted after controlling for multiple comparisons.
The large proportion of missing or unknown R/E data and low overall rate of performance on these quality measures made the relevance of small differences difficult to determine. This analysis demonstrates the feasibility of using the Axon Registry to assess neurologic disparities in outpatient care. More education and training are required on the accurate capture of R/E data in the EHR
Climate variability and simultaneous breadbasket yield shocks as observed in long-term yield records
No full text•A dataset of >34,000 yield observations from 25 countries dating back to 1900 is used.•ENSO, the IOD, and NAO all affect the probability of simultaneous yield shocks by 20–40%.•The NAO affects the overall number of global wheat yield shocks most strongly.•ENSO affects the pattern of global simultaneous maize yield shocks most strongly.•There were fewer simultaneous yield shocks during 1975–2017 as compared to 1931–1975.That climate variability and change can potentially force multiple simultaneous breadbasket crop yield shocks has been established. But research quantifying the mechanisms behind such simultaneous shocks has been constrained by short records of crop yields. Here we compile a dataset of subnational crop yields in 25 countries dating back to 1900 to study the frequency and trends in multiple breadbasket yield shocks and how large-scale climate anomalies on interannual timescales have affected multiple breadbasket yield shocks over the last century. We find that major simultaneous breadbasket yield shocks have occurred in at least three, four, or five of nine breadbaskets 10.3%, 2.3% and 1.1% of the time for maize and 18.4%, 4.6% and 2.3% of the time for wheat. Furthermore, we find that multiple breadbasket yield shocks decreased in frequency even as those breadbaskets experience increasingly frequent climate-related shocks. For both maize and wheat breadbaskets, there were fewer simultaneous yield shocks during the 1975–2017 time period as compared to 1931–1975. Finally, we find that interannual modes of climate variability - such as the El Niño Southern Oscillation (ENSO), the Indian Ocean Dipole (IOD), and the North Atlantic Oscillation (NAO) - have all affected the relative probability of simultaneous yield shocks in pairs of breadbaskets by up to 20–40% in both maize and wheat breadbaskets. While past literature has focused on the effects of ENSO, we find that at the global scale the NAO affects the overall number of wheat yield shocks most strongly despite only affecting northern hemisphere breadbaskets
HIV Promotes Atherosclerosis via Circulating Extracellular Vesicle MicroRNAs
No full textPeople living with HIV (PLHIV) are at a higher risk of having cerebrocardiovascular diseases (CVD) compared to HIV negative (HIV) individuals. The mechanisms underlying this elevated risk remains elusive. We hypothesize that HIV infection results in modified microRNA (miR) content in plasma extracellular vesicles (EVs), which modulates the functionality of vascular repairing cells, i.e., endothelial colony-forming cells (ECFCs) in humans or lineage negative bone marrow cells (linBMCs) in mice, and vascular wall cells. PLHIV (N = 74) have increased atherosclerosis and fewer ECFCs than HIVindividuals (N = 23). Plasma from PLHIV was fractionated into EVs (HIV) and plasma depleted of EVs (HIV PL). HIV, but not HIV PLor HIV(EVs from HIVindividuals), increased atherosclerosis inmice, which was accompanied by elevated senescence and impaired functionality of arterial cells and linBMCs. Small RNA-seq identified EV-miRs overrepresented in HIV, including let-7b-5p. MSC (mesenchymal stromal cell)-derived tailored EVs (TEVs) loaded with the antagomir for let-7b-5p (miRZip-let-7b) counteracted, while TEVs loaded with let-7b-5p recapitulated the effects of HIVin vivo. LinBMCs overexpressing(a let-7b-5p target gene) lacking the 3'UTR and as such is resistant to miR-mediated regulation showed protection against HIV-induced changes in linBMCs in vitro. Our data provide a mechanism to explain, at least in part, the increased CVD risk seen in PLHIV
Role of antioxidants in itch treatment: lessons learned from pain management
No full textByline: Georgia Biazus Soares, Dr. Philip Frost Department of Dermatology and Cutaneous Surgery, Miami Itch Center, University of Miami Miller School of Medicine, Miami, FL; Omar Mahmoud; Gil Yosipovitch Chronic pain and chronic pruritus are both debilitating conditions that cause a significant burden to patients. Oxidative stress--driven by an imbalance between reactive oxygen species and antioxidants--has been shown to play a role both in pain disorders and conditions in which chronic itch is a prominent symptom. Antioxidants can be useful in treating oxidative stress-driven diseases and have shown promise in treating chronic pain conditions such as fibromyalgia and osteoarthritis. However, their role in treating pruritus and pruritic conditions such as psoriasis and atopic dermatitis remains unclear. Many of the current treatments for chronic itch are costly, associated with side effects, and have limited efficacy. Therefore, further controlled studies exploring antioxidants as a potential therapeutic option for chronic pruritus are warranted.Academi