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1.
J Clin Neurosci ; 125: 7-11, 2024 May 10.
Article En | MEDLINE | ID: mdl-38733901

This study measures the impact of preoperative motor weakness (MW) on Patient-Reported Outcome Measures (PROMs) in lateral lumbar interbody fusion (LLIF) patients. Retrospectively-sourced data from a prospectively-maintained, single-surgeon database created two cohorts of LLIF patients: patients with/without documented MW. Demographics/perioperative characteristics/PROMs were collected preoperatively and at six-weeks/final follow-up (FF). Studied outcomes were Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF), 12-Item Short Form (SF-12) Physical/Mental Component Score (PCS/MCS), Patient Health Questionnaire (PHQ-9), Visual Analog Scale Back/Leg Pain (VAS-BP/LP), and Oswestry Disability Index (ODI). Multivariable linear/logistic regression calculated/compared intercohort minimum clinically important difference (MCID). Mean postoperative follow-up time was 11.5 ± 7.52 months. In total, 214 LLIF patients from December 2010 to May 2023 were included, with 149 having documented MW. In Table 1, self-reported gender was significant between cohorts (p < 0.025). Other significant demographic characteristics were smoker status (p < 0.002), diabetes (p < 0.016), and CCI score (p < 0.011). Table 2 shows notably significant perioperative characteristics: spinal pathology (degenerative spondylolisthesis/foraminal stenosis/herniated nucleus pulposus) (p < 0.005, all), estimated blood loss/length of stay/postoperative day (POD)-zero narcotic consumption (p < 0.001, all). Table 3 outcomes/MCID achievement percentages demonstrated insignificant intercohort differences besides a weakly significant FF ODI score (p < 0.036). MW, a frequently reported symptom in spine surgery, is poorly studied in LLIF patients. Thus, this study evaluates MW impact on PROMs and notes no significant differences. However, one exception regarding FF disability scores was recorded. MW did not affect MCID achievement for our patient population. Therefore, the preliminary findings suggest preoperative MW imparts minimal influence on PROMs/MCID in LLIF patients.

2.
J Neurosci ; 2024 May 07.
Article En | MEDLINE | ID: mdl-38719449

Decreased neuronal specificity of the brain in response to cognitive demands (i.e., neural dedifferentiation) has been implicated in age-related cognitive decline. Investigations into functional connectivity analogues of these processes have focused primarily on measuring segregation of nonoverlapping networks at rest. Here, we used an edge-centric network approach to derive entropy, a measure of specialization, from spatially overlapping communities during cognitive task fMRI. Using Human Connectome Project Lifespan data (713 participants, 36-100 years old, 55.7% female), we characterized a pattern of nodal despecialization differentially affecting the medial temporal lobe and limbic, visual, and subcortical systems. At the whole-brain level, global entropy moderated declines in fluid cognition across the lifespan and uniquely covaried with age when controlling for the network segregation metric modularity. Importantly, relationships between both metrics (entropy and modularity) and fluid cognition were age-dependent, although entropy's relationship with cognition was specific to older adults. These results suggest entropy is a potentially important metric for examining how neurological processes in aging affect functional specialization at the nodal, network, and whole-brain level.Significant Statement Many potential clinical applications of fMRI necessitate examining localized function to assess and guide behavioral, pharmacological, surgical, and neuromodulatory interventions. Edge-community entropy offers the mathematical and conceptual advantage of calculating the functional specialization of individual nodes within an overlapping and interdependent system of communities using whole-brain, temporally-informed data. We suggest entropy during cognitive tasks may be a more conceptually appropriate functional connectivity analogue of age-related neural dedifferentiation than network segregation metrics, and demonstrate entropy strongly correlates with age and moderates cognition. Notably, entropy was strongly related to age at the whole-brain level and more strongly related than participation coefficient at the nodal level, offering greater potential to interrogate how local age-related dysfunction influences distributed systems supporting cognition and behavior.

3.
Article En | MEDLINE | ID: mdl-38700750

Background: Packed red blood cell (PRBC) transfusion has been shown to increase nosocomial infection risk in the injured population; however, the post-traumatic infectious risk profiles of non-PRBC blood products are less clear. We hypothesized that plasma (fresh frozen plasma [FFP]), platelet (PLT), and cryoprecipitate administration would not be associated with increased rates of nosocomial infections. Patients and Methods: We performed a retrospective, matched, case-control study utilizing the American College of Surgeons National Trauma Data Bank data for 2019. We included all patients who received any volume of PRBC within four hours of presentation. Our outcome of interest was any infection. Controls were matched to cases using individual matching with a desired 1:3 case:control ratio. Bivariable analysis according to infection status, and multivariable logistic regression modeling the development of infection were then performed upon the matched data. Results: A total of 1,563 infectious cases were matched to 3,920 non-infectious controls. First four-hour transfusion volumes for FFP, PLT, and cryoprecipitate in the infection group exceeded those in the control group. The first four-hour FFP transfusion volume (per unit odds ratio [OR], 1.02; 95% confidence interval [CI], 0.99-1.04; p = 0.28) and cryoprecipitate transfusion volume (per unit OR, 1.01; 95% CI, 0.99-1.02; p = 0.43) were similar in cases and controls whereas PLT transfusion volume (per unit OR, 0.92; 95% CI, 0.86-0.98; p = 0.01) was lower in cases of infection than in controls. Conclusions: Fresh frozen plasma, PLT, and cryoprecipitate transfusion volumes were not independent risk factors for the development of nosocomial infection in a trauma population. PLT transfusion volume was associated with less infection.

4.
PeerJ ; 12: e17345, 2024.
Article En | MEDLINE | ID: mdl-38708346

Ecological niche divergence is generally considered to be a facet of evolution that may accompany geographic isolation and diversification in allopatry, contributing to species' evolutionary distinctiveness through time. The null expectation for any two diverging species in geographic isolation is that of niche conservatism, wherein populations do not rapidly shift to or adapt to novel environments. Here, I test ecological niche divergence for a widespread, pan-American lineage, the avian genus of martins (Progne). The genus Progne includes migrant and resident species, as well as geographically restricted taxa and widespread, intercontinentally distributed taxa, thus providing an ideal group in which to study the nature of niche divergence within a broad geographic mosaic. I obtained distributional information for the genus from publicly available databases and created ecological niche models for each species to create pairwise comparisons of environmental space. I combined these data with the most up-to-date phylogeny of Progne currently available to examine the patterns of niche evolution within the genus. I found limited evidence for niche divergence across the breeding distributions of Progne, and much stronger support for niche conservatism with patterns of niche partitioning. The ancestral Progne had a relatively broad ecological niche, like extant basal Progne lineages, and several geographically localized descendant species occupy only portions of this larger ancestral niche. I recovered strong evidence of breeding niche divergence for four of 36 taxon pairs but only one of these divergent pairs involved two widespread species (Southern Martin P. elegans vs. Gray-breasted Martin P. chalybea). Potential niche expansion from the ancestral species was observed in the most wide-ranging present-day species, namely the North American Purple Martin P. subis and P. chalybea. I analyzed populations of P. subis separately, as a microcosm of Progne evolution, and again found only limited evidence of niche divergence. This study adds to the mounting evidence for niche conservatism as a dominant feature of diversifying lineages, and sheds light on the ways in which apparently divergent niches may arise through allopatry while not involving any true niche shifts through evolutionary time. Even taxa that appear unique in terms of habitat or behavior may not be diversifying with respect to their ecological niches, but merely partitioning ancestral niches among descendant taxa.


Ecosystem , Phylogeny , Animals , Biological Evolution , Passeriformes/classification , Passeriformes/physiology , Birds
5.
JAMA ; 331(17): 1496-1499, 2024 05 07.
Article En | MEDLINE | ID: mdl-38587828

This cohort study characterizes heterogeneity in cardiac function prior to sepsis and describes associations with hospitalization outcomes and mortality.


Sepsis , Humans , Heart/physiopathology , Prognosis
6.
J Vasc Surg ; 2024 Apr 10.
Article En | MEDLINE | ID: mdl-38608964

OBJECTIVE: The aim of this study was to evaluate the 5-year outcomes of fenestrated/branched endovascular aortic repair (F/BEVAR) for the treatment of complex aortic aneurysms stratified by the aneurysm extent. METHODS: Patients with the diagnosis of complex aortic aneurysm, who underwent F/BEVAR at a single center were included in this study and retrospectively analyzed. The cohort was divided according to the aneurysm extent, comparing group 1 (types I-III thoracoabdominal aneurysms [TAAAs]), group 2 (type IV TAAAs), and group 3 (juxtarenal [JRAAs], pararenal [PRAAs], or paravisceral [PVAAs] aortic aneurysms). The primary endpoints were 30-day and 5-year survival. The secondary endpoints were technical success, occurrence of spinal cord ischemia, primary patency of the visceral arteries, freedom from target vessel instability, and secondary interventions. RESULTS: Of 436 patients who underwent F/BEVAR between July 2012 and May 2023, 131 presented with types I to III TAAAs, 69 with type IV TAAAs, and 236 with JRAAs, PRAAs, or PVAAs. All cases were treated under a physician-sponsored investigational device exemption protocol with a patient-specific company-manufactured or off-the-shelf device. Group 1 had significantly younger patients than group 2 or 3 respectively (69.6 ± 8.7 vs 72.4 ± 7.1 vs 73.2 ± 7.3 years; P < .001) and had a higher percentage of females (50.4% vs 21.7% vs 17.8%; P < .001). Prior history of aortic dissection was significantly more common among patients in group 1 (26% vs 1.4% vs 0.9%; P < .001), and mean aneurysm diameter was larger in group 1 (64.5 vs 60.7 vs 63.2 mm; P = .033). Comorbidities were similar between groups, except for coronary artery disease (P < .001) and tobacco use (P = .003), which were less prevalent in group 1. Technical success was similar in the three groups (98.5% vs 98.6% vs 98.7%; P > .99). The 30-day mortality was 4.5%, 1.4%, and 0.4%, in groups 1, 2, and 3, respectively, and was significantly higher in group 1 when compared with group 3 (P = .01). The incidence of spinal cord ischemia was significantly higher in group 1 compared with group 3 (5.3% vs 4.3% vs 0.4%; P = .004). The 5-year survival was significantly higher in group 3 when compared with group 1 (P = .01). Freedom from secondary intervention was significantly higher in group 3 when compared with group 1 (P = .003). At 5 years, there was no significant difference in freedom from target vessel instability between groups or primary patency in the 1652 target vessels examined. CONCLUSIONS: Larger aneurysm extent was associated with lower 5-year survival, higher 30-day mortality, incidence of secondary interventions, and spinal cord ischemia. The prevalence of secondary interventions in all groups makes meticulous follow-up paramount in patients with complex aortic aneurysm treated with F/BEVAR.

7.
Stem Cell Res Ther ; 15(1): 119, 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38659070

BACKGROUND: Adipose stromal cells (ASC) are a form of mesenchymal stromal cells that elicit effects primarily via secreted factors, which may have advantages for the treatment of injury or disease. Several previous studies have demonstrated a protective role for MSC/ASC on mitigating acute kidney injury but whether ASC derived factors could hasten recovery from established injury has not been evaluated. METHODS: We generated a concentrated secretome (CS) of human ASC under well-defined conditions and evaluated its ability to improve the recovery of renal function in a preclinical model of acute kidney injury (AKI) in rats. 24 h following bilateral ischemia/reperfusion (I/R), rats were randomized following determination of plasma creatinine into groups receiving vehicle -control or ASC-CS treatment by subcutaneous injection (2 mg protein/kg) and monitored for evaluation of renal function, structure and inflammation. RESULTS: Renal function, assessed by plasma creatinine levels, recovered faster in ASC-CS treated rats vs vehicle. The most prominent difference between the ASC-CS treated vs vehicle was observed in rats with the most severe degree of initial injury (Pcr > 3.0 mg/dl 24 h post I/R), whereas rats with less severe injury (Pcr < 2.9 mg/dl) recovered quickly regardless of treatment. The quicker recovery of ASC-treated rats with severe injury was associated with less tissue damage, inflammation, and lower plasma angiopoietin 2. In vitro, ASC-CS attenuated the activation of the Th17 phenotype in lymphocytes isolated from injured kidneys. CONCLUSIONS: Taken together, these data suggest that ASC-CS represents a potent therapeutic option to improve established AKI.


Acute Kidney Injury , Inflammation , Acute Kidney Injury/therapy , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Animals , Rats , Humans , Inflammation/pathology , Inflammation/metabolism , Male , Secretome/metabolism , Adipose Tissue/cytology , Adipose Tissue/metabolism , Rats, Sprague-Dawley , Injections, Subcutaneous , Kidney/metabolism , Kidney/pathology , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Reperfusion Injury/metabolism , Reperfusion Injury/therapy , Stromal Cells/metabolism
8.
Cell Death Discov ; 10(1): 175, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38622136

Papillary thyroid carcinoma (PTC) is the most frequent form of thyroid cancer. PTC commonly presents with mutations of the serine/threonine kinase BRAF (BRAFV600E), which drive ERK1/2 pathway activation to support growth and suppress apoptosis. PTC patients often undergo surgical resection; however, since the average age of PTC patients is under 50, adverse effects associated with prolonged maintenance therapy following total thyroidectomy are a concern. The development of mutant-selective BRAF inhibitors (BRAFi), like vemurafenib, has been efficacious in patients with metastatic melanoma, but the response rate is low for mutant BRAF PTC patients. Here, we assay the therapeutic response of BRAFi in a panel of human PTC cell lines and freshly biopsied patient samples. We observed heterogeneous responses to BRAFi, and multi-omic comparisons between susceptible and resistant mutant BRAF PTC revealed overrepresented stress response pathways and the absence of compensatory RTK activation - features that may underpin innate resistance. Importantly, resistant cell lines and patient samples had increased hallmarks of failed apoptosis; a cellular state defined by sublethal caspase activation and DNA damage. Further analysis suggests that the failed apoptotic phenotypes may have features of "minority mitochondrial outer membrane permeabilization (MOMP)" - a stress-related response characterized by fragmented and porous mitochondria known to contribute to cancer aggressiveness. We found that cells presenting with minority MOMP-like phenotypes are dependent on the apoptotic regulator, Mcl-1, as treatment with the Mcl-1 inhibitor, AZD5991, potently induced cell death in resistant cells. Furthermore, PI3K/AKT inhibitors sensitized resistant cells to BRAFi; an effect that was at least in part associated with reduced Mcl-1 levels. Together, these data implicate minority MOMP as a mechanism associated with intrinsic drug resistance and underscore the benefits of targeting Mcl-1 in mutant BRAF PTC.

9.
PLoS One ; 19(4): e0298327, 2024.
Article En | MEDLINE | ID: mdl-38626151

BACKGROUND: An elevated shock index (SI) predicts worse outcomes in multiple clinical arenas. We aimed to determine whether the SI can aid in mortality risk stratification in unselected cardiac intensive care unit patients. METHODS: We included admissions to the Mayo Clinic from 2007 to 2015 and stratified them based on admission SI. The primary outcome was in-hospital mortality, and predictors of in-hospital mortality were analyzed using multivariable logistic regression. RESULTS: We included 9,939 unique cardiac intensive care unit patients with available data for SI. Patients were grouped by SI as follows: < 0.6, 3,973 (40%); 0.6-0.99, 4,810 (48%); and ≥ 1.0, 1,156 (12%). After multivariable adjustment, both heart rate (adjusted OR 1.06 per 10 beats per minute higher; CI 1.02-1.10; p-value 0.005) and systolic blood pressure (adjusted OR 0.94 per 10 mmHg higher; CI 0.90-0.97; p-value < 0.001) remained associated with higher in-hospital mortality. As SI increased there was an incremental increase in in-hospital mortality (adjusted OR 1.07 per 0.1 beats per minute/mmHg higher, CI 1.04-1.10, p-Value < 0.001). A higher SI was associated with increased mortality across all examined admission diagnoses. CONCLUSION: The SI is a simple and universally available bedside marker that can be used at the time of admission to predict in-hospital mortality in cardiac intensive care unit patients.


Intensive Care Units , Humans , Hospital Mortality , Retrospective Studies , Blood Pressure , Heart Rate
10.
bioRxiv ; 2024 Apr 11.
Article En | MEDLINE | ID: mdl-38645136

Genome instability is a hallmark of cancer and are driven by mutations in oncogenes and tumor suppressor genes. Despite successes seen with select targeted therapeutics, this type of personalized medicine is only beneficial for a small subpopulation of cancer patients who have one of a few actionable genetic changes. Most tumors also contain hundreds of passenger mutations that offered no fitness advantage or disadvantage during tumor evolution. Mutations in known pharmacogenetic (PGx) loci for which germline variants encode variability in drug response can cause somatically acquired drug sensitivity. The NUDT15 gene is a known PGx locus that participates in the rate-limiting metabolism of thiopurines. People with two defective germline alleles of NUDT15 are hypersensitive to the toxic effects of thiopurines. NUDT15 is located adjacent to the Retinoblastoma ( RB1 ) tumor suppressor gene, which often undergoes homozygous deletion in retinoblastomas and other epithelial cancers. We observed that RB1 undergoes homozygous deletions in 9.4% of prostate adenocarcinomas and 2.5% of ovarian cancers, and in nearly all of these cases NUDT15 is also lost. Moreover, 44% of prostate adenocarcinomas and over 60% of ovarian cancers have lost one allele of NUDT15, which predicts that a majority of all prostate and ovarian cancers have somatically acquired hypersensitivity to thiopurine treatment. We performed a retrospective analysis of >16,000 patients in the US Veterans Administration health care system and found concurrent xanthine oxidase inhibition (XOi) and thiopurine usage for non-cancer indications is significantly associated with reduced incidence of prostate cancer. The hazard ratio for the development of prostate cancer in patients treated with thiopurines and XOi was 0.562 (0.301-1.051) for the unmatched cohort and 0.389 (0.185-0.819) for the propensity score matched cohort. We experimentally depleted NUDT15 from ovarian and prostate cancer cell lines and observed a dramatic sensitization to thiopurine-induced and DNA damage-dependent toxicity. These results indicate that somatic loss of NUDT15 predicts therapeutic sensitivity to a low cost and well tolerated drug with a broad therapeutic window.

11.
Cardiol Clin ; 42(2): 195-213, 2024 May.
Article En | MEDLINE | ID: mdl-38631790

The acute aortic syndromes (AAS) are life-threatening vascular compromises within the aortic wall. These include aortic dissection (AD), intramural hematoma (IMH), penetrating aortic ulcer (PAU), and blunt traumatic thoracic aortic injury (BTTAI). While patients classically present with chest pain, the presentation may be highly variable. Timely diagnosis is critical to initiate definitive treatment and maximize chances of survival. In high-risk patients, treatment should begin immediately, even while diagnostic evaluation proceeds. The mainstay of medical therapy is acute reduction of heart rate and blood pressure. Surgical intervention is often required but is informed by patient anatomy and extent of vascular compromise.


Aortic Diseases , Aortic Dissection , Humans , Aortic Diseases/diagnosis , Triage , Aorta
13.
BMC Surg ; 24(1): 110, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38622597

BACKGROUND: The reporting of surgical instrument errors historically relies on cumbersome, non-automated, human-dependent, data entry into a computer database that is not integrated into the electronic medical record. The limitations of these reporting systems make it difficult to accurately estimate the negative impact of surgical instrument errors on operating room efficiencies. We set out to determine the impact of surgical instrument errors on a two-hospital healthcare campus using independent observers trained in the identification of Surgical Instrument Errors. METHODS: This study was conducted in the 7 pediatric ORs at an academic healthcare campus. Direct observations were conducted over the summer of 2021 in the 7 pediatric ORs by 24 trained student observers during elective OR days. Surgical service line, error type, case type (inpatient or outpatient), and associated length of delay were recorded. RESULTS: There were 236 observed errors affecting 147 individual surgical cases. The three most common errors were Missing+ (n = 160), Broken/poorly functioning instruments (n = 44), and Tray+ (n = 13). Errors arising from failures in visualization (i.e. inspection, identification, function) accounted for 88.6% of all errors (Missing+/Broken/Bioburden). Significantly more inpatient cases (42.73%) had errors than outpatient cases (22.32%) (p = 0.0129). For cases in which data was collected on whether an error caused a delay (103), over 50% of both IP and OP cases experienced a delay. The average length of delays per case was 10.16 min. The annual lost charges in dollars for surgical instrument associated delays in chargeable minutes was estimated to be between $6,751,058.06 and $9,421,590.11. CONCLUSIONS: These data indicate that elimination of surgical instrument errors should be a major target of waste reduction. Most observed errors (88.6%) have to do with failures in the visualization required to identify, determine functionality, detect the presence of bioburden, and assemble instruments into the correct trays. To reduce these errors and associated waste, technological advances in instrument identification, inspection, and assembly will need to be made and applied to the process of sterile processing.


Operating Rooms , Surgical Instruments , Humans , Child , Hospitals
14.
J Pediatr Surg ; 2024 Mar 14.
Article En | MEDLINE | ID: mdl-38584009

BACKGROUND: Hirschsprung-associated enterocolitis (HAEC) is the most common cause of morbidity and mortality in patients with Hirschsprung disease (HD). There is a correlation between social determinants of health (SDOH) and outcomes in children with HD. The Child Opportunity Index (COI) is a publicly available dataset that stratifies patients by address into levels of opportunity. We aimed to understand if a relationship exists between COI and HAEC. METHODS: A single-institution, IRB-approved, retrospective cohort study was performed of children with HD. Census tract information was used to obtain COI scores, which were stratified into categories (very low, low, medium, high, very high). Subgroups with and without history of HAEC were compared. RESULTS: The cohort had 100 patients, of which 93 had a COI score. There were 27 patients (29.0%) with HAEC. There were no differences in demographics or clinical factors, including length of aganglionic colon, operative approach, and age at pull-through. As child opportunity score increased from very low to very high, there was a statistically significant decrease in the incidence of HAEC (p = 0.04). CONCLUSION: We demonstrate a significant association between increasing opportunity and decreasing incidence of HAEC. This suggests an opportunity for targeted intervention in populations with low opportunity. LEVEL OF EVIDENCE: III. IRB NUMBER: IRB14-00232.

15.
Circ Heart Fail ; 2024 Apr 08.
Article En | MEDLINE | ID: mdl-38587438

Background: Associations of early changes in vasoactive support with cardiogenic shock (CS) mortality remain incompletely defined. Methods: The Critical Care Cardiology Trials Network is a multicenter registry of cardiac intensive care units (CICUs). Patients admitted with CS (2018-2023) had vasoactive dosing assessed at 4 and 24 hours (h) from CICU admission and quantified by the vasoactive-inotropic score (VIS). Prognostic associations of VIS at both timepoints, as well as change in VIS from 4h to 24h, were examined. Interaction testing was performed by mechanical circulatory support (MCS) status. Results: Among 3,665 patients, 82% had a change in VIS <10, with 7% and 11% having a ≥10point increase and decrease from 4h to 24h, respectively. The 4h and 24h VIS were each associated with CICU mortality (13%- 45% and 11%-73% for VIS <10 to ≥40, respectively; ptrend <0.0001 for each). Stratifying by the 4h VIS, changes in VIS from 4h to 24h had a graded association with mortality, ranging from a 2-to->4-fold difference in mortality comparing those with a ≥10-point increase to a ≥10-point decrease in VIS (p-trend <0.0001). The change in VIS alone provided good discrimination of CICU mortality (C-statistic 0.72 [95% CI 0.70-0.75]), and improved discrimination of the 24h SOFA score (0.76 [95% CI 0.74-0.78] from 0.72 [95% CI 0.69-0.74]) and the clinician-assessed SCAI stage (0.77 [95% CI 0.75-0.79] from 0.72 [95% CI 0.70-0.74]). Although present in both groups, the mortality risk associated with VIS was attenuated in patients managed with vs. without MCS (OR per 10-point higher 24h VIS: 1.36 [1.23-1.49] vs. 1.84 [1.69-2.01]; p-interaction<0.0001). Conclusions: Early changes in the magnitude of vasoactive support in CS are associated with a gradient of risk for mortality. These data suggest that early VIS trajectory may improve CS prognostication, with potential to be leveraged for clinical decision-making and research applications in CS.

16.
PLoS Pathog ; 20(4): e1012172, 2024 Apr.
Article En | MEDLINE | ID: mdl-38662769

The implementation of antiretroviral therapy (ART) has effectively restricted the transmission of Human Immunodeficiency Virus (HIV) and improved overall clinical outcomes. However, a complete cure for HIV remains out of reach, as the virus persists in a stable pool of infected cell reservoir that is resistant to therapy and thus a main barrier towards complete elimination of viral infection. While the mechanisms by which host proteins govern viral gene expression and latency are well-studied, the emerging regulatory functions of non-coding RNAs (ncRNA) in the context of T cell activation, HIV gene expression and viral latency have not yet been thoroughly explored. Here, we report the identification of the Cytoskeleton Regulator (CYTOR) long non-coding RNA (lncRNA) as an activator of HIV gene expression that is upregulated following T cell stimulation. Functional studies show that CYTOR suppresses viral latency by directly binding to the HIV promoter and associating with the cellular positive transcription elongation factor (P-TEFb) to activate viral gene expression. CYTOR also plays a global role in regulating cellular gene expression, including those involved in controlling actin dynamics. Depletion of CYTOR expression reduces cytoplasmic actin polymerization in response to T cell activation. In addition, treating HIV-infected cells with pharmacological inhibitors of actin polymerization reduces HIV gene expression. We conclude that both direct and indirect effects of CYTOR regulate HIV gene expression.


Gene Expression Regulation, Viral , HIV Infections , HIV-1 , RNA, Long Noncoding , Virus Latency , Humans , RNA, Long Noncoding/genetics , HIV Infections/virology , HIV Infections/genetics , HIV-1/genetics , HIV-1/physiology , Promoter Regions, Genetic , Lymphocyte Activation , Jurkat Cells
17.
AEM Educ Train ; 8(1): e10936, 2024 Feb.
Article En | MEDLINE | ID: mdl-38510727

Objectives: The objective was to develop an innovative method of training emergency medicine (EM) resident physicians to perform the head impulse test (HIT) component of the HINTS (head impulse test, nystagmus, test of skew) examination using video-oculography (VOG) device feedback. Methods: Using principles from motor learning theory and Ericsson's framework for expertise, we developed a training innovation utilizing VOG device feedback to teach the degree (10°-20°) and velocity (>100°/s) of head turn required for the HIT. We assessed the technical ability of participants to perform the HIT using the VOG device, without feedback, to count the number of successful HITs out of 20 attempts before, immediately after, and 2 weeks after the training innovation. Participants rated their confidence on a 1 to 5 Likert scale before and 2 weeks after training. Results: Most participants (11 of 14, 78%) were unable to perform even one successful HIT in 20 attempts before training despite brief verbal and visual instruction regarding the head turn parameters. However, most participants achieved more than one success, in fact, all with at least five successes, immediately after training (13 of 14, 93%) and again 2 weeks after training (nine of 11, 82%). The median (interquartile range) number of successful HITs was 0 (0, mean 0.79) during baseline testing, 7.5 (5.8) immediately after training, and 10 (8.0) 2 weeks after training (p < 0.01, Kruskal-Wallis). The median confidence rating increased from 1.5 (1) before baseline testing to 3 (1.5) after follow-up testing (p = 0.02, Mann-Whitney U). Conclusions: Prior to motor training, most participants failed to properly perform the HIT. Feedback training with VOG devices may facilitate development of the skills required to properly perform the HIT. Further study is needed to assess the ability to train the interpretive aspect of the HIT and other components of the HINTS examination.

18.
Sci Rep ; 14(1): 7034, 2024 03 25.
Article En | MEDLINE | ID: mdl-38528068

Signal processing techniques are of vital importance to bring THz spectroscopy to a maturity level to reach practical applications. In this work, we illustrate the use of machine learning techniques for THz time-domain spectroscopy assisted by domain knowledge based on light-matter interactions. We aim at the potential agriculture application to determine the amount of free water on plant leaves, so-called leaf wetness. This quantity is important for understanding and predicting plant diseases that need leaf wetness for disease development. The overall transmission of 12,000 distinct water droplet patterns on a plastized leaf was experimentally acquired using THz time-domain spectroscopy. We report on key insights of applying decision trees and convolutional neural networks to the data using physics-motivated choices. Eventually, we discuss the generalizability of these models to determine leaf wetness after testing them on cases with increasing deviations from the training set.


Machine Learning , Physics , Plant Leaves/chemistry , Water/analysis , Spectrum Analysis
19.
J Am Heart Assoc ; 13(6): e031979, 2024 Mar 19.
Article En | MEDLINE | ID: mdl-38456417

Cardiogenic shock continues to carry a high mortality rate despite contemporary care, with no breakthrough therapies shown to improve survival over the past few decades. It is a time-sensitive condition that commonly results in cardiovascular complications and multisystem organ failure, necessitating multidisciplinary expertise. Managing patients with cardiogenic shock remains challenging even in well-resourced settings, and an important subgroup of patients may require cardiac replacement therapy. As a result, the idea of leveraging the collective cognitive and procedural proficiencies of multiple providers in a collaborative, team-based approach to care (the "shock team") has been advocated by professional societies and implemented at select high-volume clinical centers. A slowly maturing evidence base has suggested that cardiogenic shock teams may improve patient outcomes. Although several registries exist that are beginning to inform care, particularly around therapeutic strategies of pharmacologic and mechanical circulatory support, none of these are currently focused on the shock team approach, multispecialty partnership, education, or process improvement. We propose the creation of a Cardiogenic Shock Team Collaborative-akin to the successful Pulmonary Embolism Response Team Consortium-with a goal to promote sharing of care protocols, education of stakeholders, and discovery of how process and performance may influence patient outcomes, quality, resource consumption, and costs of care.


Shock, Cardiogenic , Humans , Shock, Cardiogenic/diagnosis , Shock, Cardiogenic/therapy , Shock, Cardiogenic/etiology
20.
Ear Hear ; 2024 Mar 20.
Article En | MEDLINE | ID: mdl-38503724

OBJECTIVES: Vestibular vertigo has been shown to have a high lifetime prevalence. Previous studies have described the increased morbidities associated with vestibular vertigo. DESIGN: In this cross-sectional study of the 2016 National Health Interview Study, we sought to explore whether individuals with vestibular vertigo were more likely to utilize healthcare resources compared with those without vestibular vertigo. We characterized utilization of specific healthcare resources including general doctors, specialist doctors, emergency departments, mental health professionals, and others among individuals with vestibular vertigo to better understand how individuals with vertigo interact with the US healthcare system. RESULTS: In multivariable analyses, participants with vestibular vertigo had an increased number of nights in the hospital in the last 12 months (mean difference = 0.67 days, 95% confidence interval [CI] = 0.37 to 0.97), increased odds of receiving healthcare 10 or more times in the last 12 months (odds ratio = 2.22, 95% CI = 1.99 to 2.48) and increased number of visits to a healthcare professional in the last 2 weeks (mean difference = 0.17 visits, 95% CI = 0.14 to 0.21). In addition, participants with vestibular vertigo had increased odds of visiting both general doctors, specialist doctors, and other healthcare professionals. CONCLUSIONS: These findings characterize how individuals with vestibular vertigo utilize and interact with healthcare resources compared with those without vestibular vertigo.

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