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Being a PhD student is not easy.Navigating the highly competitive world of academia while working hard for little or no pay would be stressful for anyone--but it's especially challenging for graduate students who are also parents.

Background Patients undergoing total hip arthroplasty (THA) often are satisfied with the decrease in pain and improvement in function they achieve after surgery. Even so, strength and functional performance deficits persist after recovery, but these remain poorly characterized; knowledge about any ongoing strength or functional deficits may allow therapists to design rehabilitation programs to optimize recovery after THA. Questions/purposes The purposes of this study were to (1) evaluate postoperative muscle strength, function, and quality of life during the first year after THA; and (2) compare strength and function in patients 1 year after THA with a cohort of healthy peers. Methods Twenty-six patients undergoing THA were assessed 1, 3, 6, and 12 months postoperatively, and 19 adults with no hip pathology were tested as a control group. Isometric muscle strength (hip flexors, extensors, abductors, knee extensors, and flexors), functional performance (stair climbing, five times sit-to-stand, timed-up-and-go, 6-minute walk, and single-limb stance tests), and self-reported function (Hip Disability and Osteoarthritis Score, SF-36, and UCLA activity score) were compared. Results One month after THA, patients had 15% less hip flexor and extensor torque, 26% less abductor torque, 14% less knee extensor and flexor torque, and worse performance on the stair climbing, timed-up-and-go, single-limb stance, and 6-minute walk. Compared with healthy adults, patients 12 months after THA had 17% less knee extensor and 23% less knee flexor torque; however, the functional testing (including stair climbing, five times sit-to-stand, and the 6-minute walk) showed no significant differences with the patient numbers available between individuals undergoing THA and healthy control subjects. SF-36 Physical Component Scores, although significantly improved from preoperative levels, were significantly worse than healthy adults 1 year after THA (p < 0.01). Conclusions Patients experience early postoperative strength losses and decreased functional capacity after THA, yet strength deficits may persist after recovery. This may suggest that rehabilitation may be most effective in the first month after surgery. Level of Evidence Level II, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Approximately one in five patients undergoing coronary artery bypass graft (CABG) surgery will develop post-operative acute kidney injury (AKI). We sought to determine whether biomarkers of kidney tubule dysfunction and injury are associated with long-term risk of acute kidney injury (AKI) after coronary artery bypass graft (CABG) surgery. We performed a cohort study using data from the REasons for Geographic And Racial Differences in Stroke (REGARDS), a national, population-based, longitudinal cohort study of 30,239 U.S. adults aged ≥45 years. Of 760 REGARDS participants who underwent CABG surgery after their REGARDS baseline visit, we excluded those with a history of dialysis or kidney transplant, missing laboratory data or with illegible or erroneous records, leaving 394 in the analysis. Exposures included urinary biomarkers of kidney tubule dysfunction (urine alpha-1 microglobulin [A1M], uromodulin [UMOD] and epidermal growth factor [EGF]) and injury (kidney injury molecule-1 [KIM-1]), measured at an average of 5.5 years before CABG surgery. The primary outcome was AKI development following CABG surgery, defined as an increase in serum creatinine ≥0.3 mg/dL from 48 hours prior to CABG surgery to end of hospitalization. Of 394 participants, 176 (45%) experienced post-CABG surgery AKI. Higher baseline urine A1M was associated with higher odds of AKI (adjusted OR 1.34 per 2-fold higher A1M, 95% Confidence Interval (CI): 1.00-1.80). Higher urine UMOD was associated with lower odds of AKI (adjusted OR 0.77 per 2-fold higher UMOD, 95% CI 0.62-0.95). Higher EGF showed a tendency towards lower odds of AKI (adjusted OR 0.79 per 2-fold higher EGF, 95% CI 0.59-1.05). KIM-1 was not associated with AKI (adjusted OR 0.92 per 2-fold higher KIM-1, 95% CI 0.77-1.10). Select biomarkers of kidney tubule dysfunction, but not injury, are associated with future risk of AKI after CABG surgery. Biomarkers measured years before surgery may predict post-CABG surgery AKI.

Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases. Whole exome sequencing of patients who experienced severe influenza reveals several genes, including scaffold protein AHNAK, with predicted loss-of-function variants that are also identified in our proteomic analyses. Of our identified host factors, 54 significantly alter IAV infection upon siRNA knockdown, and two factors, AHNAK and coatomer subunit COPB1, are also essential for productive infection by SARS-CoV-2. Finally, 16 compounds targeting our identified host factors suppress IAV replication, with two targeting CDK2 and FLT3 showing pan-antiviral activity across influenza and coronavirus families. This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT. Using a multi-OMICS approach, Haas et al identify 54 human genes and 16 host-targeting chemical compounds that regulate influenza A virus infection in lung epithelial cells, including AHNAK and COBP1 which are also essential for SARS-CoV-2 infection.

Non-typhoidal Salmonella (NTS) is a leading cause of bloodstream infections in Africa, but the various contributions of host susceptibility versus unique pathogen virulence factors are unclear. We used data from a population-based surveillance platform (population ~25,000) between 2007-2014 and NTS genome-sequencing to compare host and pathogen-specific factors between individuals presenting with NTS bacteremia and those presenting with NTS diarrhea. Salmonella Typhimurium ST313 and Salmonella Enteritidis ST11 were the most common isolates. Multi-drug resistant strains of NTS were more commonly isolated from patients presenting with NTS bacteremia compared to NTS diarrhea. This relationship was observed in patients under age five [aOR = 15.16, 95% CI (2.84-81.05), P = 0.001], in patients five years and older, [aOR = 6.70 95% CI (2.25-19.89), P = 0.001], in HIV-uninfected patients, [aOR = 21.61, 95% CI (2.53-185.0), P = 0.005], and in patients infected with Salmonella serogroup B [aOR = 5.96, 95% CI (2.28-15.56), P < 0.001] and serogroup D [aOR = 14.15, 95% CI (1.10-182.7), P = 0.042]. Thus, multi-drug-resistant NTS was strongly associated with bacteremia compared to diarrhea among children and adults. This association was seen in HIV-uninfected individuals infected with either S. Typhimurium or S. Enteritidis. Risk of developing bacteremia from NTS infection may be driven by virulence properties of the Salmonella pathogen.

Unilateral breast erythema, edema, and are classically associated with inflammatory breast cancer. However, occasionally this constellation of symptoms is seen with other causes. Maintaining a broad differential can therefore save a prospective patient from months of worry about a possible cancer diagnosis, untreated symptoms, and unnecessary and expensive tests. Here we present the case of a 75-year-old woman with a history of pacemaker placement complicated by left upper extremity deep venous thrombosis (DVT) who subsequently developed left breast , swelling, and erythema. After initially being worked up for inflammatory breast cancer, including multiple breast biopsies, she was then referred to specialists in cardiology, allergy, pulmonology, rheumatology, dermatology, lymphedema therapy, and vascular surgery undergoing an exhaustive workup that spanned nearly a year. Eventually, a venogram was performed, which revealed complete occlusion of her left subclavian vein. After undergoing angioplasty and stenting, her symptoms resolved.

Objectives/Goals: To identify lipid signatures associated with adverse pregnancy outcomes (APOs) and postpartum weight retention (PPWR) in women entering pregnancy with overweight or obesity and to explore potential epigenetic mechanisms through ongoing DNA methylation (DNAm) analysis. Methods/Study Population: The GROWell: Goals for Reaching Optimal Wellness study was a blinded, randomized clinical trial to improve dietary support during pregnancy and postpartum. Data were collected via online questionnaires, electronic health records (EHRs), and participant-collected dried blood spots (DBS) at 10–16 weeks, 36–38 weeks, and 3 months postpartum. We analyzed DBS data from 49 participants using three lipidomic analytical techniques: weighted lipid correlation network analysis, differential lipid analysis, and partial least squares discriminant analysis. Lipid profiles were characterized and then tested for associations with APOs and PPWR at all three time points. DNAm analysis from the samples is ongoing to determine the epigenetic mechanisms associated with lipid dysregulation and pregnancy outcomes. Results/Anticipated Results: The lipid network analysis revealed positive correlations between specific lipid types and APOs, particularly at 10–16 weeks and postpartum. Notably, triglycerides and phosphatidylcholine were associated with an increased risk of APOs. Additionally, in the third trimester, triglycerides were positively correlated with weight-related variables. Postpartum analysis also showed a positive correlation between elevated triglyceride levels and a history of APOs. The network analysis also revealed positive associations between triglycerides and PPWR, which were most evident at the 36–38 week and postpartum time points. Ongoing methylation analysis is expected to identify genomic regions associated with pregnancy outcomes. Discussion/Significance of Impact: These findings underscore the significant role of lipids in pregnancy outcomes for individuals with overweight or obesity. Identifying lipidomic and methylome biomarkers of risk for APOs and PPWR may help with early detection and intervention, improving maternal and fetal health.

Robust COVID-19 outcomes classification is important for ongoing epidemiology research on acute and post-acute COVID-19 conditions. Protocolized medical record review is an established method to validate endpoints for clinical trials and cardiovascular epidemiology cohorts; however, a protocol to adjudicate hospitalizations for COVID-19 among epidemiology cohorts was lacking. We developed a protocol to ascertain and adjudicate hospitalized COVID-19 across a meta-cohort of 14 US prospective cohort studies. This report describes the first three years of protocol implementation (October 1, 2020-October 1, 2023) and evaluates its repeatability and performance compared to classification by administrative codes. The protocol was adapted from cohort approaches to clinical cardiovascular events ascertainment and adjudication. Potential COVID-19 hospitalizations and deaths were identified by self-/proxy-report and, in some cases, active surveillance. Medical records were requested from hospitals and adjudicated for COVID-19 outcomes by clinically trained personnel according to a standardized rubric. Inter-rater agreement was assessed. The sensitivity and specificity of discharge diagnosis codes was compared to adjudicated diagnoses. The study obtained medical records for 1,167 potential COVID-19 hospitalizations, which underwent protocolized adjudication. Adjudication confirmed COVID-19 infection was present for 1,030 (88%) events, of which COVID-19 was not the cause of hospitalization for 78 (8%). Of 952 hospitalizations determined by adjudicators to be caused by COVID-19, 319 (34%) participants were critically ill and 210 (22%) died. Pneumonia was confirmed in 822 (86%) and acute kidney injury in 350 (37%); other cardiovascular and thrombotic complications were rare (2-5%). Interrater reliability among adjudicators was high (kappa = 0.85-1.00) except for myocardial infarction (kappa = 0.60). Compared to adjudication, sensitivity of discharge diagnosis codes was higher for pneumonia (84%) and pulmonary embolism (81%) than for other complications (48-70%). Protocolized adjudication confirmed four out of five COVID-19 hospitalizations in a US meta-cohort and confirmed cases of pneumonia, pulmonary embolism, and other conditions that were not indicated by discharge diagnosis codes. These results highlight the importance of validating health outcomes for use in research on COVID-19 and post-COVID-19 conditions, and some limitations of claims-based data.

Syncope is a common chief complaint among older adults in the Emergency Department (ED), and orthostatic vital signs are often a part of their evaluation. We assessed whether abnormal orthostatic vital signs in the ED are associated with composite 30-day serious outcomes in older adults presenting with syncope. We performed a secondary analysis of a prospective, observational study at 11 EDs in adults ≥ 60 years who presented with syncope or near syncope. We excluded patients lost to follow up. We used the standard definition of abnormal orthostatic vital signs or subjective symptoms of lightheadedness upon standing to define orthostasis. We determined the rate of composite 30-day serious outcomes, including those during the index ED visit, such as cardiac arrhythmias, myocardial infarction, cardiac intervention, new diagnosis of structural heart disease, stroke, pulmonary embolism, aortic dissection, subarachnoid hemorrhage, cardiopulmonary resuscitation, hemorrhage/anemia requiring transfusion, with major traumatic injury from fall, recurrent syncope, and death) between the groups with normal and abnormal orthostatic vital signs. The study cohort included 1974 patients, of whom 51.2% were male and 725 patients (37.7%) had abnormal orthostatic vital signs. Comparing those with abnormal to those with normal orthostatic vital signs, we did not find a difference in composite 30-serious outcomes (111/725 (15.3%) vs 184/1249 (14.7%); unadjusted odds ratio, 1.05 [95%CI, 0.81–1.35], p = 0.73). After adjustment for gender, coronary artery disease, congestive heart failure (CHF), history of arrhythmia, dyspnea, hypotension, any abnormal ECG, physician risk assessment, medication classes and disposition, there was no association with composite 30-serious outcomes (adjusted odds ratio, 0.82 [95%CI, 0.62–1.09], p = 0.18). In a cohort of older adult patients presenting with syncope who were able to have orthostatic vital signs evaluated, abnormal orthostatic vital signs did not independently predict composite 30-day serious outcomes.