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Distribution and administration strategy are critical to successful population immunization efforts. Agent-based modeling (ABM) can reflect the complexity of real-world populations and can experimentally evaluate vaccine strategy and policy. However, ABMs historically have been limited in their time-to-development, long runtime, and difficulty calibrating. Our team had several technical advances in the development of our GradABMs: a novel class of scalable, fast and differentiable simulations. GradABMs can simulate million-size populations in a few seconds on commodity hardware, integrate with deep neural networks and ingest heterogeneous sources. This allows for rapid and real-world sensitivity analyses. Our first epidemiological GradABM (EpiABMv1) enabled simulation interventions over real million-scale populations and was used in vaccine strategy and policy during the COVID-19 pandemic. Literature suggests decisions aided by evidence from these models saved thousands of lives. Our most recent model (EpiABMv2) extends EpiABMv1 to allow improved regional calibration using deep neural networks to incorporate local population data, and in some cases different policy recommendations versus our prior models. This is an important advance for our model to be more effective at vaccine strategy and policy decisions at the local public health level., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Alcohol use disorder (AUD) is a highly prevalent health issue in the United States. The number of those receiving medication-assisted treatment (MAT) is limited, despite strong evidence for their effectiveness. The inpatient setting may represent an important opportunity to initiate MAT. The goal of this study was to summarize the data on naltrexone initiation in the emergency department or inpatient setting for the management of AUDs. We searched ClinicalTrials.gov, Ovid EBM Reviews, Ovid Embase, Ovid Medline, Ovid PsycINFO, Scopus, and Web of Science from inception through October 31, 2019. Search strategies were created using a combination of keywords (Supplemental Appendix 1, available online at http://www.mcpiqojournal.org) and standardized index terms related to naltrexone therapy for medically hospitalized patients with AUD. Two uncontrolled pre-post study designs evaluated naltrexone prescription rates, 30-day readmission rates, and rehospitalization rates. Two authors independently abstracted data on study characteristics, results, and study-level risk of bias. The research team collaborated to assess the strength of evidence across studies. Two studies reported that implementing a protocol for naltrexone initiation increased MAT rates, with one study noting a substantial decrease in 30-day hospital readmissions. Overall, we found that there is a paucity of data on naltrexone initiation in the inpatient setting for AUDs. This likely reflects the nature of current clinical practice and prescriber comfortability. There is a need for further studies evaluating MAT initiation in the inpatient setting. Furthermore, efforts to increase provider knowledge of these therapeutic options are in need of further exploration., (© 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

Objective: To identify demographic trends associated with patient utilization and healthcare provider request for spiritual care services and to describe the impact of spiritual care on the quality of life (QoL), spiritual well-being (SWB) and level of satisfaction (SAT) of hospitalized patients., Patients and Methods: A systematic search of Ovid MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, was combined with review of relevant bibliographies. A total of 464 titles and abstracts were reviewed. Data were independently extracted by reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data on the effects of spiritual interventions on QoL, SWB and SAT were extracted, along with demographic data reflecting chaplain services. The results of the studies are presented narratively and in a qualitative manner., Results: Observational or experimental studies investigating chaplain utilization demographics (n = 12), patient satisfaction (n = 9) and QoL/SWB (n = 3) were included. Perceived severity of illness, average length of stay and older age were consistently found to be predictors of higher need for spiritual care. Receipt of spiritual care was correlated with increased patient and family satisfaction, independent of clinical outcome. Chaplain interventions were associated with improvement in perceived QoL and SWB. In spite of this, healthcare workers rarely attempt to explore the patient's or family's need for spiritual care, with the majority of chaplaincy consults occurring in the final day of the patient's life, potentially leading to a failure to meet the spiritual needs of non-terminal patients who have spiritual trauma related to their resolving illnesses., Conclusion: Attention to the spiritual needs of hospitalized patients is an essential yet often overlooked aspect of patient care. Chaplains serve as spiritual care specialists whose services can enhance the hospital experience, improve patient satisfaction and help to bridge potential gaps between the patient and medical providers.

Objectives: Inappropriate use of telemetry monitoring is associated with alarm fatigue, an increase in health care expenditures, and the potential for patient harm from interventions in clinically inconsequential arrhythmias. We explored adherence to current guidelines for appropriateness of (1) initial telemetry assignment and (2) duration of the assignment., Study Design: Retrospective study., Methods: After institutional review board approval, 695 consecutive adult patients (≥ 18 years) who were admitted with any diagnosis to general medical floors and assigned telemetry at the time of admission over 3 months were enrolled. Patients on surgical service and transferred from critical care were excluded. Data were collected from electronic health records (EHRs)., Results: We observed that 155 of 695 (22.3%) patients had been inappropriately assigned telemetry at the time of initial assignment. Of the 540 patients appropriately assigned telemetry, 56.3% of patients had longer than the recommended duration of telemetry monitoring with a median (interquartile range) of 3 (2-4) nonindicated days per patient. The annualized additional cost of telemetry monitoring due to the inefficient utilization was found to be more than $500,000 per year., Conclusions: Our data further support the need for frequent reassessment of telemetry indication, which can be facilitated by the utilization of EHR-based automated monitoring.

The human gut is colonized by a community of microbiota, primarily bacteria, that exist in a symbiotic relationship with the host. Intestinal microbiota-host interactions play a critical role in the regulation of human physiology. Deleterious changes to the composition of gut microbiota, referred to as gut dysbiosis, has been linked to the development and progression of numerous diseases, including cardiovascular disease (CVD). Imbalances in host-microbial interaction impair homeostatic mechanisms that regulate health and can activate multiple pathways leading to CVD risk factor progression. Most CVD risk factors, including aging, obesity, dietary patterns, and a sedentary lifestyle, have been shown to induce gut dysbiosis. Dysbiosis is associated with intestinal inflammation and reduced integrity of the gut barrier, which in turn increases circulating levels of bacterial structural components and microbial metabolites, including trimethylamine-N-oxide and short-chain fatty acids, that may facilitate the development of CVD. This article reviews the normal function and composition of the gut microbiome, mechanisms leading to the leaky gut syndrome, its mechanistic link to CVD and potential novel therapeutic approaches aimed towards restoring gut microbiome and CVD prevention. As CVD is the leading cause of deaths globally, investigating the gut microbiota as a locus of intervention presents a novel and clinically relevant avenue for future research., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Syncope forms a major part of medical in-flight emergencies contributing one-in-four in-flight medical events accounting to 70% of flight diversions. In such patients, it is important to elucidate the pathophysiology of syncope prior to diversion. Postural hypotension is the most common etiology of in-flight syncopal events. However, individuals without any underlying autonomic dysfunction can still experience syncope from hypoxia also known as airline syncope. Initial steps in managing such patients include positioning followed by the airway, breathing and circulation of resuscitation. These interventions need to be in close coordination with ground control to determine decision for flight diversion. Interventions which have been tried for prevention include mental challenge and increased salt and fluid intake. The current paper enhances the understanding of airline syncope by summarizing the associated pathophysiologic mechanisms and the management medical personnel can initiate with limited resources., Competing Interests: Conflict-of-interest statement: All authors report no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To explore the role of venous thromboembolism (VTE) risk reassessment in hospitalized medically ill patients without a change in level of care., Patients and Methods: In this exploratory retrospective study, the medical records of 171 consecutive adult patients (≥18 years) hospitalized under the medicine service for more than 3 days without a change in the level of care from January 1, 2015, to March 1, 2015, were reviewed. The primary outcome was a change in the risk score between day 1 and day 3 of hospital stay (using the Padua Prediction Score). The secondary outcomes were changes in risk stratification class (low vs high) and cost-benefit analysis., Results: The risk score was significantly different between day 1 and day 3 (4.7±1.7 vs 4.2±1.8; P =.008). All the patients with low risk on day 1 remained at low risk on day 3. However, 25 of 136 patients (18.4%) with high risk on day 1 were reclassified as low risk on day 3 ( P <.001). No patients changed from low risk to high risk at day 3. The reclassification could have saved $35 per patient-day of inappropriate pharmacological prophylaxis in addition to patient discomfort, bleeding risk, and heparin-induced thrombocytopenia., Conclusion: This is the first study to suggest the need for regular assessment for VTE risk on medicine wards because of changing patient risk. Regular reassessment could reduce health care waste and patient discomfort., (© 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

Stroke is a chronic condition and a leading cause of disability. After hospital discharge, patients need to transition into home-based rehabilitation, a long and distressful process. However, they are often ill-prepared to manage recovery at home; and many are socially isolated. There is a growing number of stroke patients who utilize social media platforms, YouTube in particular, to publish video blogs (vlogs) to make their stories heard and to share their rehabilitation experience. In this study, we analyzed 246 such YouTube vlogs to better understand this new form of patient story-telling and its value to vloggers, viewers, as well as healthcare professionals. We found that vlogging helps stroke patients overcome physical and speech constraints to self-journal, and to connect with other people online. Based on these findings, we discuss how future health systems may leverage vlogs to design self-tracking technologies, to generate patient health data, and to offer patient-centered education.

Tripartite motif containing 28 (TRIM28) is a transcriptional regulator acting as an essential corepressor for Krüppel-associated box zinc finger domain-containing proteins in multiple tissue and cell types. An increasing number of studies have investigated the function of TRIM28; however, its prognostic value in breast cancer (BC) remains unclear. In the present study, the expression of TRIM28 was identified to be significantly higher in cancerous compared with healthy tissue samples. Furthermore, it was demonstrated that TRIM28 expression was significantly correlated with several clinicopathological characteristics of patients with BC, such as p53 mutation, tumor recurrence and Elston grade of the tumor. In addition, a protein-protein interaction network was created to illustrate the interactions of TRIM28 with other proteins. The prognostic value of TRIM28 in patients with BC was investigated using the Kaplan-Meier Plotter database, which revealed that high expression of TRIM28 is a predictor of poor prognosis in patients with BC. In conclusion, the results of the present study indicate that TRIM28 provides a survival advantage to patients with BC and is a novel prognostic biomarker, in addition to being a therapeutic target for the treatment of BC.

With the completion of the nucleotide sequences of several complex eukaryotic genomes, tens of thousands of genes have been predicted. However, this information has to be correlated with the functions of those genes to enhance our understanding of biology and to improve human health care. The Drosophila transposon P-element-induced mutations are very useful for directly connecting gene products to their biological function. We designed an efficient transposon P-element-mediated gene disruption procedure and performed genetic screening for single P-element insertion mutations, enabling us to recover 2500 lethal mutations. Among these, 2355 are second chromosome mutations. Sequences flanking >2300 insertions that identify 850 different genes or ESTs (783 genes on the second chromosome and 67 genes on the third chromosome) have been determined. Among these, 455 correspond to genes for which no lethal mutation has yet been reported. The Drosophila genome is thought to contain approximately 3600 vital genes; 1400 are localized on the second chromosome. Our mutation collection represents approximately 56% of the second chromosome vital genes and approximately 24% of the total vital Drosophila genes.

Etanercept is the first anticytokine drug approved to treat rheumatoid arthritis. Side effects are infrequent, the most common being local skin reactions, headaches, and upper respiratory tract symptoms. We report the first case of lung injury that occurred while receiving this agent. Biopsy specimens of lung and skin lesions demonstrated noncaseating granulomas associated with a microscopic particulate. Withdrawal of etanercept achieved clinical stabilization, and the addition of prednisone resulted in rapid improvement.

The temporal bones from a 58-year-old white woman who had had hereditary congenital deafness were examined with the techniques of microdissection and surface preparations followed by sectioning of the modiolus. There was bilateral, almost total sensorineural degeneration, which also involved the saccule. The degeneration of the distal processes of the cochlear neurons in the osseous spiral lamina was almost complete, whereas numerous ganglion cells and proximal processes remained in the modiolus and the internal auditory canal. Severe cochleo-saccular hydrops was present in the left ear with Reissner's membrane bulging into the horizontal canal. X-ray diffraction and electron probe analysis were used to study the abnormal crystalline deposits in both ears. On the left side the saccular otoconia were composed of calcite, but the utricular macula was covered by a crust of apatite spherulites. More apatite occurred around the maculae and in the scala media. The cupulae were composed of apatite and octacalcium phosphate. On the right side the utricular otoconia were of normal calcite, but there was a deposit of apatite on the macula sacculi. The upper part of the scala media was completely filled by a deposit of apatite and octacalcium phosphate.

Four variations and degrees of severity of the Mondini malformation were found in the temporal bones from two neonates, one with congenital heart disease and the other with trisomy D, and from one teenager with leukemia: 1) short cochlea and normal vestibular organs; 2) short cochlea and persistent horizontal canal anlage; 3) markedly shortened cochlea with no modiolus, wide internal auditory meatus, and persistent horizontal canal anlage; 4) same as variation 3, but with persistent anlagen in all semicircular canals. Variations 3 and 4 were from the case of trisomy D, in which the left cochlea had a normal hair cell population but few nerve fibers, and the intraganglionic spiral bundle was displaced from Rosenthal's canal to the osseous spiral lamina. The right ear had no cochlear nerve fibers; the organ of Corti was present, but hair cells were unusually small. In the case of trisomy D, both ears showed subtotal loss of vestibular nerve fibers. Although the rudimentary cristae of the right ear had numerous hair cells, the macular hair cells were fewer and malformed. No hydrops was present.

Temporal bones from five patients with hearing loss as a result of aminoglycoside treatment were examined by the method of microdissection and surface preparations, followed by celloidin embedding and serial sectioning of the modiolus. Three patients had received the newer antibiotics, gentamicin, tobramycin, and amikacin; the other two neomycin. In the cochleas from two patients of the first group there was only a small loss of hair cells, restricted to the lower end of the basal turn. The third, who had been treated with several antibiotics over a longer period of time, showed more extensive but strikingly asymmetrical patterns of degeneration in the two ears. This patient, as well as the fourth, who had received neomycin during peritoneal lavage, had numerous patchy areas of complete disappearance of Corti's organ in the basal turn, with incipient degeneration of the distal ends of the nerve fibers in adjacent portions of the osseous spiral lamina. The fifth patient, who had become deaf after prolonged treatment with neomycin by mouth, showed a complete loss of cochlear hair cells. Nerve fibers were present only in the middle and upper turns, where supporting cells remained. Midmodiolar sections showed a proportionately much greater loss of the distal than of the proximal processes of the cells of the spiral ganglion. These findings underscore once again the special hazard for the inner ear that is associated with the clinical use of neomycin, regardless of the route of administration.

A small intracochlear neurinoma was found in the temporal bone of a 54-year-old man who had no history of hearing loss or dizziness. The tumor was small, confined to the scala tympani, and did not visibly alter the tissues around it. The neurinoma was derived from the distal processes of the cochlear neuron. Intralabyrinthine tumors can cause auditory and vestibular symptoms and are difficult to diagnose.

Utilizing normal patient blood samples, two automated differential pattern recognition systems, the ADC-500 and the Hematrak 360, were compared in a duplicate study with the manual eye method, using spun and wedge smear preparations. The study showed a superior precision for the 500-cell differential, but occasional data points with spun smears were unusually drifted from the central cluster for both the manual and instrument methods. Analysis of the data uncovered at least two reasons for these unusual outliers: "star artifacts" and warped glass slides. The importrance of these method-related artifacts are discussed, alo ng with the future of the 500-cell differential with today's automated technology.

Chemical substances migrate outwards from within the body to the skin surface by diffusion from cutaneous capillaries across the epidermis. Heretofore, study of transepidermal chemical emissions have been restricted to substances which are in the vapor phase at skin surface temperature. We have investigated outward transcutaneous chemical migration of nongaseous chemicals by devising an occlusive transcutaneous chemical collection system, consisting of a tape-encased plug of gelled saline in which activated carbon is dispersed. Investigations of nine chemicals in 'fuzzy' rats, rhesus monkeys, and man provide data which are consistent with a general theory of outward transcutaneous chemical migration. This noninvasive continuous transcutaneous sampling technique provides a new method for investigating skin permeability in vivo and may provide a basis for convenient diagnosis and monitoring of chemical exposure.