Abstract Background Our purpose was to determine the relationship between preoperative frailty and the occurrence of postoperative complications after colorectal and cardiac operations. Methods ...Patients 65 years or older undergoing elective colorectal or cardiac surgery were enrolled. Seven baseline frailty traits were measured preoperatively: Katz score less than or equal to 5, Timed Up and Go test greater than or equal to 15 seconds, Charlson Index greater than or equal to 3, anemia less than 35%, Mini-Cog score less than or equal to 3, albumin less than 3.4 g/dL, and 1 or more falls within 6 months. Patients were categorized by the number of positive traits as follows: nonfrail: 0 to 1 traits, prefrail: 2 to 3 traits, and frail: 4 or more traits. Results Two hundred one subjects (age 74 ± 6 years) were studied. Preoperative frailty was associated with increased postoperative complications after colorectal (nonfrail: 21%, prefrail: 40%, frail: 58%; P = .016) and cardiac operations (nonfrail: 17%, prefrail: 28%, frail: 56%; P < .001). This finding in both groups was independent of advancing age. Frail individuals in both groups had longer hospital stays and higher 30-day readmission rates. Receiver operating characteristic curves examining frailty's ability to forecast complications were colorectal (.702, P = .004) and cardiac (.711, P < .001). Conclusions A simple preoperative frailty score defines older adults at higher risk for postoperative complications across surgical specialties.
Abstract Background The purpose of this study was to determine the relationship of frailty and 6-month postoperative costs. Methods Subjects aged ≥ 65 years undergoing elective colorectal operations ...were enrolled in a prospective observational study. Frailty was assessed by a validated measure of function, cognition, nutrition, comorbidity burden, and geriatric syndromes. Frailty was quantified by summing the number of positive characteristics in each subject. Results Sixty subjects (mean age, 75 ± 8 years) were studied. Inpatient mortality was 2% (n = 1). Overall, 40% of subjects (n = 24) were considered nonfrail, 22% (n = 13) were prefrail, and 38% (n = 22) were frail. With advancing frailty, hospital costs increased ( P < .001) and costs from discharge to 6-months increased ( P < .001). Higher degrees of frailty were related to increased rates of discharge institutionalization ( P < .001) and 30-day readmission ( P = .044). Conclusions A simple, brief preoperative frailty assessment accurately forecasts increased surgical hospital costs and postdischarge to 6-month healthcare costs after colorectal operations in older adults.
Lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis involve the progressive and inexorable destruction of oxygen exchange surfaces and airways, and have emerged as a ...leading cause of death worldwide. Mitigating therapies, aside from impractical organ transplantation, remain limited and the possibility of regenerative medicine has lacked empirical support. However, it is clinically known that patients who survive sudden, massive loss of lung tissue from necrotizing pneumonia or acute respiratory distress syndrome often recover full pulmonary function within six months. Correspondingly, we recently demonstrated lung regeneration in mice following H1N1 influenza virus infection, and linked distal airway stem cells expressing Trp63 (p63) and keratin 5, called DASC(p63/Krt5), to this process. Here we show that pre-existing, intrinsically committed DASC(p63/Krt5) undergo a proliferative expansion in response to influenza-induced lung damage, and assemble into nascent alveoli at sites of interstitial lung inflammation. We also show that the selective ablation of DASC(p63/Krt5) in vivo prevents this regeneration, leading to pre-fibrotic lesions and deficient oxygen exchange. Finally, we demonstrate that single DASC(p63/Krt5)-derived pedigrees differentiate to type I and type II pneumocytes as well as bronchiolar secretory cells following transplantation to infected lung and also minimize the structural consequences of endogenous stem cell loss on this process. The ability to propagate these cells in culture while maintaining their intrinsic lineage commitment suggests their potential in stem cell-based therapies for acute and chronic lung diseases.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The assembly status of the V. cholerae flagellum regulates biofilm formation, suggesting that the bacterium senses a lack of movement to commit to a sessile lifestyle. Motility and biofilm formation ...are inversely regulated by the second messenger molecule cyclic dimeric guanosine monophosphate (c-di-GMP). Therefore, we sought to define the flagellum-associated c-di-GMP-mediated signaling pathways that regulate the transition from a motile to a sessile state. Here we report that elimination of the flagellum, via loss of the FlaA flagellin, results in a flagellum-dependent biofilm regulatory (FDBR) response, which elevates cellular c-di-GMP levels, increases biofilm gene expression, and enhances biofilm formation. The strength of the FDBR response is linked with status of the flagellar stator: it can be reversed by deletion of the T ring component MotX, and reduced by mutations altering either the Na+ binding ability of the stator or the Na+ motive force. Absence of the stator also results in reduction of mannose-sensitive hemagglutinin (MSHA) pilus levels on the cell surface, suggesting interconnectivity of signal transduction pathways involved in biofilm formation. Strains lacking flagellar rotor components similarly launched an FDBR response, however this was independent of the status of assembly of the flagellar stator. We found that the FDBR response requires at least three specific diguanylate cyclases that contribute to increased c-di-GMP levels, and propose that activation of biofilm formation during this response relies on c-di-GMP-dependent activation of positive regulators of biofilm production. Together our results dissect how flagellum assembly activates c-di-GMP signaling circuits, and how V. cholerae utilizes these signals to transition from a motile to a sessile state.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Frailty is a state of increased vulnerability to health-related stressors and can be measured by summing the number of frailty characteristics present in an individual. Discharge ...institutionalization (rather than discharge to home) represents disease burden and functional dependence after hospitalization. Our aim was to determine the relationship between frailty and need for postoperative discharge institutionalization. Study Design Subjects ≥65 years undergoing major elective operations requiring postoperative ICU admission were enrolled. Discharge institutionalization was defined as need for institutionalized care at hospital discharge. Fourteen preoperative frailty characteristics were measured in 6 domains: comorbidity burden, function, nutrition, cognition, geriatric syndromes, and extrinsic frailty. Results A total of 223 subjects (mean age 73 ± 6 years) were studied. Discharge institutionalization occurred in 30% (n = 66). Frailty characteristics related to need for postoperative discharge institutionalization included: older age, Charlson index ≥3, hematocrit <35%, any functional dependence, up-and-go ≥15 seconds, albumin <3.4 mg/dL, Mini-Cog score ≤3, and having fallen within 6 months (p < 0.0001 for all comparisons). Multivariate logistic regression retained prolonged timed up-and-go (p < 0.0001) and any functional dependence (p < 0.0001) as the variables most closely related to need for discharge institutionalization. An increased number of frailty characteristics present in any one subject resulted in increased rate of discharge institutionalization. Conclusions Nearly 1 in 3 geriatric patients required discharge to an institutional care facility after major surgery. The frailty characteristics of prolonged up-and-go and any functional dependence were most closely related to the need for discharge institutionalization. Accumulation of a higher number of frailty characteristics in any one geriatric patient increased their risk of discharge institutionalization.
We propose a novel method for privacy-preserving training of deep neural networks leveraging public, out-domain data. While differential privacy (DP) has emerged as a mechanism to protect sensitive ...data in training datasets, its application to complex visual recognition tasks remains challenging. Traditional DP methods, such as Differentially-Private Stochastic Gradient Descent (DP-SGD), perform well only on simple datasets and shallow networks, while recent transfer learning-based DP methods often make unrealistic assumptions about the availability and distribution of public data. In this work, we argue that minimizing the number of trainable parameters is the key to improving the privacy-performance tradeoff of DP on complex visual recognition tasks. Inspired by this argument, we also propose a novel transfer learning paradigm that finetunes a very sparse subnetwork with DP. We conduct extensive experiments and ablation studies on two visual recognition tasks: CIFAR-100 → CIFAR-10 (standard DP setting) and the CD-FSL challenge (few-shot, multiple levels of domain shifts) and demonstrate competitive experimental performance.
Many dynamic biological processes are regulated by protein–protein interactions and protein localization. Experimental techniques to probe such processes with temporal and spatial precision include ...photoactivatable proteins and chemically induced dimerization (CID) of proteins. CID has been used to study several cellular events, especially cell signaling networks, which are often reversible. However, chemical dimerizers that can be both rapidly activated and deactivated with high spatiotemporal resolution are currently limited. Herein, we present a novel chemical inducer of protein dimerization that can be rapidly turned on and off using single pulses of light at two orthogonal wavelengths. We demonstrate the utility of this molecule by controlling peroxisome transport and mitotic checkpoint signaling in living cells. Our system highlights and enhances the spatiotemporal control offered by CID. This tool addresses biological questions on subcellular levels by controlling protein–protein interactions.
Background Preoperative risk stratification is commonly performed by assessing end-organ function (such as cardiac and pulmonary) to define postoperative risk. Little is known about impaired ...preoperative cognition and outcomes. The purpose of this study was to evaluate the impact of baseline impaired cognition on postoperative outcomes in geriatric surgery patients. Study Design Subjects 65 years and older undergoing a planned elective operation requiring postoperative ICU admission were recruited prospectively. Preoperative baseline cognition was assessed using the validated Mini-Cog test. Impaired cognition was defined as a Mini-Cog score of ≤3. Delirium was assessed using the Confusion Assessment Method-ICU by a trained research team. Adverse outcomes were defined using the Veterans Affairs Surgical Quality Improvement Program definitions. Results One hundred and eighty-six subjects were included, with a mean age of 73 ± 6 years. Eighty-two subjects (44%) had baseline impaired cognition. The impaired cognition group had the following unadjusted outcomes: increased incidence of 1 or more postoperative complications (41% vs 24%; p = 0.011), higher incidence of delirium (78% vs 37%; p < 0.001), longer hospital stays (15 ± 14 vs 9 ± 9 days; p = 0.001), higher rate of discharge institutionalization (42% vs 18%; p = 0.001), and higher 6-month mortality (13% vs 5%; p = 0.040). Adjusting for potential confounders determined by univariate analysis, logistic regression found impaired cognition was still associated with the occurrence of 1 or more postoperative complications (odds ratio = 2.401; 95% CI, 1.185−4.865; p = 0.015). Kaplan-Meier survival analysis revealed higher mortality in the impaired cognition group (log-rank p = 0.008). Conclusions Baseline cognitive impairment in older adults undergoing major elective operations is related to adverse postoperative outcomes including increased complications, length of stay, and long-term mortality. Improved understanding of baseline cognition and surgical outcomes can aid surgical decision making in older adults.
Sperm identification and selection is an essential task when processing human testicular samples for in vitro fertilization. Locating and identifying sperm cell(s) in human testicular biopsy samples ...is labor intensive and time consuming. We developed a new computer-aided sperm analysis (CASA) system, which utilizes deep learning for near human-level performance on testicular sperm extraction (TESE), trained on a custom dataset. The system automates the identification of sperm in testicular biopsy samples. A dataset of 702 de-identified images from testicular biopsy samples of 30 patients was collected. Each image was normalized and passed through glare filters and diffraction correction. The data were split 80%, 10%, and 10% into training, validation, and test sets, respectively. Then, a deep object detection network, composed of a feature extraction network and object detection network, was trained on this dataset. The model was benchmarked against embryologists' performance on the detection task. Our deep learning CASA system achieved a mean average precision (mAP) of 0.741, with an average recall (AR) of 0.376 on our dataset. Our proposed method can work in real time; its speed is effectively limited only by the imaging speed of the microscope. Our results indicate that deep learning-based technologies can improve the efficiency of finding sperm in testicular biopsy samples.
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