Electronic Health Record-Based Algorithm for Monitoring Respiratory Virus-Like Illness.

Viral respiratory illness surveillance has traditionally focused on single pathogens (e.g., influenza) and required fever to identify influenza-like illness (ILI). We developed an automated system applying both laboratory test and syndrome criteria to electronic health records from 3 practice groups in Massachusetts, USA, to monitor trends in respiratory viral-like illness (RAVIOLI) across multiple pathogens. We identified RAVIOLI syndrome using diagnosis codes associated with respiratory viral testing or positive respiratory viral assays or fever. After retrospectively applying RAVIOLI criteria to electronic health records, we observed annual winter peaks during 2015-2019, predominantly caused by influenza, followed by cyclic peaks corresponding to SARS-CoV-2 surges during 2020-2024, spikes in RSV in mid-2021 and late 2022, and recrudescent influenza in late 2022 and 2023. RAVIOLI rates were higher and fluctuations more pronounced compared with traditional ILI surveillance. RAVIOLI broadens the scope, granularity, sensitivity, and specificity of respiratory viral illness surveillance compared with traditional ILI surveillance.

COVID-19 Severity in People With HIV Compared With Those Without HIV.

BACKGROUND: People with HIV (PWH) may be at risk for more severe COVID-19 outcomes. We compared risk for severe COVID-19 in PWH with matched individuals without HIV. METHODS: We identified adults in Massachusetts with a positive SARS-CoV-2 test, March 2020-July 2022, using electronic medical record data from 3 large clinical practice groups. We then used regression models to compare outcomes among PWH versus propensity score-matched people without HIV (matched 20:1) for severe COVID-19 (pneumonia or acute respiratory distress syndrome), hospitalization, and hospital length of stay. RESULTS: We identified 171,058 individuals with COVID-19; among them, 768 PWH were matched to 15,360 individuals without HIV. Overall, severe COVID-19 and hospitalization were similar in PWH and those without HIV (severe COVID-19: 3.8% vs 3.0%, adjusted odds ratio [OR] 1.27, 95% confidence interval [CI]: 0.86-1.87; hospitalization: 12.1% vs 11.3%, adjusted OR: 1.08, 95% CI: 0.87 to 1.35). Compared with people without HIV, PWH with low CD4 T-cell counts (<200 cells/mm 3 ) had more severe COVID-19 (adjusted OR: 3.99, 95% CI: 2.06 to 7.74) and hospitalization (adjusted OR: 2.26, 95% CI: 1.35 to 3.80), but PWH with high CD4 counts had lower odds of hospitalization (adjusted OR: 0.73, 95% CI: 0.52 to 1.03). CONCLUSIONS: PWH with low CD4 T-cell counts had worse COVID-19 outcomes compared with people without HIV, but outcomes for those with high CD4 counts were similar to, or better than, those without HIV. It is unclear whether these findings are generalizable to settings where PWH have less access to and engagement with health care.

Computational assessment and in vitro test of phytochemicals of Usnea aciculifera as potential inhibitors of Escherichia coli efflux pump AcrB.

Lichens produce secondary metabolites that have many pharmaceutical activities such as antimicrobial, antioxidant, antiviral, anticancer, antigenotoxic, anti-inflammatory, analgesic and antipyretic activities. However, there is limited research on their efflux pump inhibitory activities. Twelve phytochemicals were isolated from Usnea aciculifera, and their activity of AcrAB-TolC efflux pump inhibition was evaluated. Four potential compounds, which are diffractaic acid (2), 8' -O- methylstictic acid (5), 3-hydroxy-4-(methoxycarbonyl)-2,5-dimethylphenyl 2,4-dimethoxy-3,6-dimethylbenzoate (8) and 3-hydroxy-4-(methoxycarbonyl)-2,5-dimethylphenyl 2-hydroxy-4-methoxy-3,6-dimethylbenzoate (9), were found by virtual screening using pharmacophore and 2D-QSAR model. Compound 8 exhibited AcrB inhibition activity in vitro with an accumulation H33342 percentage compared with untreated control of 202% at a concentration of 50 µM and increased the antibacterial activity of levofloxacin by four-fold at a concentration of 200 µM. By molecular docking and molecular dynamics (MD) simulation, the binding affinity of depside and depsidone derivatives to AcrB was also clarified. Despite the poor docking score to the AcrB binding site, compound 8 was the most stable among the four complexes at 20 ns of MD simulation. The analysis of long MD at 100 ns indicated that compound 8 interacts strongly with the residues in the distal pocket, creating a stable complex with ΔGbind of -31.51 kcal.mol-1. According to the ADMETlab 2.0 web server's predictions of pharmacokinetics and toxicities, compound 8 has the potential for drug development.Communicated by Ramaswamy H. Sarma.

Identification of efflux pump inhibitors for Pseudomonas aeruginosa MexAB-OprM via ligand-based pharmacophores, 2D-QSAR, molecular docking, and molecular dynamics approaches.

Efflux pumps have been reported as one of the significant mechanisms by which bacteria evade the effects of multiple antibiotics. The tripartite efflux pump MexAB-OprM in Pseudomonas aeruginosa is one of the most significant multidrug efflux systems due to its broad resistance to antibiotics such as chloramphenicol, fluoroquinolones, lipophilic ß-lactam antibiotics, nalidixic acid, novobiocin, rifampicin, and tetracycline. A promising strategy to overcome this resistance mechanism is to combine antibiotics with efflux pump inhibitors (EPIs), which can increase their intracellular concentration to enhance their biological activities. Based on 143 EPIs with chemically diverse skeletons, the 3D pharmacophore and 2D-QSAR modelings were developed and used for the virtual screening on 9.2 million compounds including ZINC15, DrugBank, and Traditional Chinese Medicine databases to identify new EPIs. The molecular docking was also performed to evaluate the binding affinity of potential EPIs to the distal-binding pocket of MexB and resulted in 611 potential EPIs. The structure-activity relationship analyses suggested that nitrogen heterocyclic compounds, piperazine and pyridine scaffolds, and amide derivatives are the most favorable chemically features for MexAB inhibitory activities. The results from molecular dynamics analysis in 100 ns indicated that ZINC009296881 and ZINC009200074 were the most potential MexB inhibitors with strong binding affinity to the distal pocket and MM/GBSA ∆Gbind values of - 38.97 and - 30.19 kcal mol-1, respectively. The predicted pharmacokinetic properties and toxicity of these compounds indicated their potential oral drugs. Multistep virtual screening of EPIs for MexAB-OprM, efflux pump multidrug resistant of P. aeruginosa.

Factors related to COVID-19 vaccine hesitancy among middle-income and low-income adults in the USA.

BACKGROUND: Vaccine hesitancy has been an ongoing challenge in campaigns, especially the rapid development and approval of the COVID-19 vaccines. The goal of this study was to understand the characteristics, perceptions and beliefs of COVID-19 vaccination prior to its widespread rollout among middle-income and low-income US adults. METHODS: Using a national sample of 2101 adults who completed an online assessment in 2021, this study examines the association of demographics, attitudes and behaviours related to COVID-19 vaccination intentions. Adaptive least absolute shrinkage and selection operator models were used to select these specific covariate and participant responses. Poststratification weights were generated using raking procedures and applied to improve generalisability. RESULTS AND CONCLUSION: Vaccine acceptance was high at 76% with 66.9% reporting intent to receive the COVID-19 vaccine when available. Only 8.8% of vaccine supporters screened positive for COVID-19-related stress compared with 9.3% among the vaccine hesitant. However, there were more people with vaccine hesitancy who screened positive for poor mental health and alcohol and substance misuse. The three main vaccine concerns were side effects (50.4%), safety (29.7%) and mistrust of vaccine distribution (14.8%).Factors influencing vaccine acceptance included age, education, children, region, mental health and social support, threat perception, opinion of governmental response, risk exposure and prevention activities and rejecting COVID-19 vaccine concerns. The results indicated acceptance was more strongly associated with beliefs and attitudes about the vaccine than sociodemographics, which are noteworthy and may lead to targeted interventions to increase COVID-19 vaccine acceptance among subgroups who are vaccine hesitant.

Discovery of AcrAB-TolC pump inhibitors: Virtual screening and molecular dynamics simulation approach.

AcrAB-TolC tripartite efflux pump, which belongs to the RND superfamily, is a main multi-drug efflux system of Escherichia coli (E. coli) because of the broad resistance on various antibiotics. With the discovering of efflux pump inhibitors (EPIs), a combination between these and antibiotics is one of the most promising therapies. Therefore, building a virtual screening model with prediction capacities for the efflux pump inhibitory activities of candidates from DrugBank and ZINC15 dataset, is one of the key goals of this project. Based on the database of 170 diverse chemical structures collected from 28 research journals, two 2D-QSAR models and a 3D-pharmacophore model have been performed. On the AcrB protein (PDB 4DX7), two binding sites have been discovered that match to the hydrophobic trap in the distal pocket and the switch loop in the proximal pocket. After virtual screening processes, twenty candidate AcrAB-TolC inhibitors have been subjected to molecular dynamics simulations, binding free energy calculations and ADMET predictions. The results indicate that three compounds namely DB09233, DB02581, and DB15224 are potential inhibitors with ΔGbind of -42.30 ± 4.58, -40.76 ± 7.30 and -31.06 ± 7.63 kcal.mol-1, respectively.Communicated by Ramaswamy H. Sarma.

Effect of a Combination of Lysolecithin, Synthetic Emulsifier and Monoglycerides on the Apparent Ileal Digestibility, Metabolizable Energy and Growth Performance of Growing Pigs.

Two studies were conducted to determine the impact of an absorption enhancer containing a combination of lysophospholipids, monoglycerides and synthetic emulsifiers (LEX) on apparent ileal digestibility, metabolizable energy (ME), and growth performance of growing pigs. In the digestibility study, 12 male crossbred [Duroc x (Large White x Landrace)] pigs with an initial body weight (BW) of 30 kg were randomly allocated to two dietary treatments: (1) a positive control (PC) receiving standard diets formulated to 3100 kcal ME/kg, and (2) a negative control formulated with −100 kcal ME/kg and −2.5% AA content vs. PC and supplemented with LEX at 500 g/t. Apparent ileal digestibility of essential AA was significantly increased for lysine, methionine, threonine, histidine, isoleucine and phenylalanine in the LEX treatment (p < 0.05). Average uplift in AA digestibility as a percent of the PC was +1.88%; with greatest improvement for histidine (+4.22%). LEX supplementation effectively compensated energy deficiency of low-density diet and provided additional ME improvement compared to the PC diet (p < 0.05). A second study was conducted to evaluate LEX dose response on the growth performance of pigs fed a low nutrient density diet. Total 450 cross-bred pigs (240 males (castrated) and 210 females) [Duroc x (Large White x Landrace)] with an average initial BW of 7.19 kg were randomly allocated into 4 dietary treatments: (1) a positive control (PC) formulated with standard specifications, (2) a negative control formulated with −100 kcal ME/kg and −2.5% AA content vs. the PC (NC), (3) NC + LEX at 250 g/t (NC + 250) and (4) NC + LEX at 500 g/t (NC + 500). Results showed significant improvement with LEX supplementation on the final BW, average daily gain (ADG) and feed conversion ratio (FCR) of pigs of >50 kg body weight. Across the study, NC + 500 significantly increased ADG vs. PC and NC, and significantly reduced FCR compared to all other treatments. FCR of negative control diets improved by 9 and 15 points with the supplementation of 250 g/t and 500 g/t of LEX, respectively (p < 0.05). FCR in the NC + 250 diet was statistically similar vs. PC, which was significantly reduced compared to the NC. Taken together, these studies demonstrate that the addition of an absorption enhancer containing a combination of lysophospholipids, monoglycerides and synthetic emulsifiers can improve growth performance in growing pigs, driven by increased nutrient digestibility and retention.

Implementation science for the adductor canal block: A new and adaptable methodology process.

BACKGROUND: Following the successful Perioperative Surgical Home (PSH) practice for total knee arthroplasty (TKA) at our institution, the need for continuous improvement was realized, including the deimplementation of antiquated PSH elements and introduction of new practices. AIM: To investigate the transition from femoral nerve blocks (FNB) to adductor canal nerve blocks (ACB) during TKA. METHODS: Our 13-month study from June 2016 to 2017 was divided into four periods: a three-month baseline (103 patients), a one-month pilot (47 patients), a three-month implementation and hardwiring period (100 patients), and a six-month evaluation period (185 patients). In total, 435 subjects were reviewed. Data within 30 postoperative days were extracted from electronic medical records, such as physical therapy results and administration of oral morphine equivalents (OME). RESULTS: Our institution reduced FNB application (64% to 3%) and increased ACB utilization (36% to 97%) at 10 mo. Patients in the ACB group were found to have increased ambulation on the day of surgery (4.1 vs 2.0 m) and lower incidence of falls (0 vs 1%) and buckling (5% vs 27%) compared with FNB patients (P < 0.05). While ACB patients (13.9) reported lower OME than FNB patients (15.9), the difference (P = 0.087) did not fall below our designated statistical threshold of P value < 0.05. CONCLUSION: By demonstrating closure of the "knowledge to action gap" within 6 mo, our institution's findings demonstrate evidence in the value of implementation science. Physician education, technical support, and performance monitoring were deemed key facilitators of our program's success. Expanded patient populations and additional orthopedic procedures are recommended for future study.

Understanding Preferences for Osteoporosis Information to Develop an Osteoporosis Patient Education Brochure.

CONTEXT: Patient education materials can provide important information related to osteoporosis prevention and treatment. However, available osteoporosis education materials fail to follow best-practice guidelines for patient education. OBJECTIVE: To develop an educational brochure on bone health for adults aged 50 years and older using mixed-method, semistructured interviews. DESIGN: This project consisted of 3 phases. In Phase 1, we developed written content that included information about osteoporosis. Additionally, we designed 2 graphic-rich brochures, Brochure A (photographs) and Brochure B (illustrations). In Phase 2, interviewers presented the text-only document and both brochure designs to 53 participants from an academic Medical Center in the Midwest and an outpatient clinic in the Southeastern region of the US. Interviewers used open- and closed-ended questions to elicit opinions regarding the brochures. In Phase 3, using feedback from Phase 2, we revised the brochure and presented it to 11 participants at a third site in the Southeastern US. MAIN OUTCOME MEASURES: Participants' comprehension of brochure text and acceptability of brochure design. RESULTS: We enrolled 64 participants. Most were women, white, and college-educated, with an average age of 66.1 years. Participants were able to restate the basic content of the brochure and preferred Brochure A's use of photographs. CONCLUSIONS: Using feedback from older adults, we developed and refined a brochure for communicating bone health information to older adults at risk of osteoporosis and fragility fractures. The methods outlined in this article may serve to guide others in developing health educational brochures for chronic medical conditions.

Vertically aligned carbon nanofibers: interconnecting solid state electronics with biosystems.

Vertically aligned carbon nanofibers (VACNFs) are grown directly on prefabricated electronic circuits with nanoscale precision. Utilizing the free-standing nanofiber array geometry, we have demonstrated the detection of nucleic acids to construct an ultrasensitive electrochemical sensor. Extending this technology towards in vivo applications, we have modified the free-standing VACNF arrays in order to achieve a multifunctional three dimensional (3-D) matrix that interpenetrates the neuronal network of PC12 cells. We found that PC12 cells cultured on the nanofiber arrays can form an extended neural network upon proper chemical and biochemical modification. The soft 3-D nanofiber array architecture provides a novel platform to fine-tune the topographical, mechanical, chemical, and electrical cues at sub-cellular scales. This biomaterial platform can be used for both fundamental studies of nanomaterial-cell interactions and the development of multifunctional, chronically stable implantable devices. The application of these devices and potential utility as a multifunctional platform for neurophysiology and biochemical studies will be discussed.

Correction of restricted extraocular muscle motility in surgical management of strabismus in graves' ophthalmopathy.

OBJECTIVE: To compare the success rates for strabismus surgery designed to correct limitation of duction with surgery designed to correct deviation in patients with Graves' ophthalmopathy. DESIGN: Retrospective nonrandomized comparative trial. PARTICIPANTS: One hundred thirty-seven patients with Graves' ophthalmopathy who had undergone at least one extraocular muscle surgery were divided into two groups: those whose first surgery occurred before June 1997 (control group) and those whose first surgery occurred in June 1997 or thereafter (case group). INTERVENTIONS: Extraocular muscle surgery primarily directed at either correcting deviation (control group) or correcting limitation of ductions (case group). MAIN OUTCOME MEASURES: Postoperative deviations in the primary position were measured in prism diopters 30 to 180 days after surgery. A postoperative deviation of less than 5 diopters was considered a successful surgical outcome. RESULTS: Patients undergoing strabismus surgery specifically designed to correct limitation of duction achieved a 74% success rate compared with a 44% success rate in the control group (P < 0.01). Furthermore, the rate of reoperation in this group was only 27% compared with 44% in the control group (P < 0.04). CONCLUSIONS: Compared with surgery aimed primarily at the correction of deviation, extraocular muscle surgery tailored to address restriction of ductions in patients with Graves' ophthalmopathy is associated with improved surgical success of initial realignment and with a lower rate of reoperation