Two self-similar Reynolds-stress transport models with anisotropic eddy viscosity.

Two Reynolds-averaged Navier-Stokes models with full Reynolds-stress transport (RST) and tensor eddy viscosity are presented. These new models represent RST extensions of the k-2L-a-C and k-ϕ-L-a-C models by Morgan [Phys. Rev. E 103, 053108 (2021)10.1103/PhysRevE.103.053108; Phys. Rev. E 105, 045104 (2022)10.1103/PhysRevE.105.045104]. Self-similarity analysis is used to derive constraints on model coefficients required to reproduce expected growth parameters for a variety of canonical flows, including Rayleigh-Taylor (RT) and Kelvin-Helmholtz (KH) mixing layers. Both models are then applied in one-dimensional simulation of RT and KH mixing layers, and the expected self-similar growth rates and anisotropy are obtained. Next, models are applied in two-dimensional simulation of the so-called "tilted rocket rig" inclined RT experiment [J. Fluids Eng. 136, 091212 (2014)10.1115/1.4027587] and in simulation of a shock-accelerated localized patch of turbulence. It is found that RST is required to capture the qualitative growth of the shock-accelerated patch, and an anisotropic eddy viscosity provides substantial improvement over a Boussinesq treatment for the tilted rocket rig problem.

Counseling Tobacco Smoke Exposure Reduction Measures in Pediatrics: A Quality Improvement Project.

With over 40% of children in the USA exposed to tobacco smoke, the AAP recommends tobacco smoke exposure (TSE) assessment during clinic visits. We aimed to increase the rates of TSE screening and provider counseling regarding TSE reduction using an evidence-based approach. Methods: We conducted the project at a large pediatric pulmonology practice. Baseline caregiver surveys and medical record review of TSE documentation took place in July/August, 2019. From September 2019 to July 2021, PDSA cycles were conducted to increase TSE screening and reduce counseling. Results: Before starting the project, 18% of smoking caregivers acknowledged smoking in the home and 41% in the car. While caregivers strongly desired to decrease TSE (median 9.4/10 on Likert scale), physician counseling of TSE reduction was offered only to 44%. PDSA cycles led to refining our patient passport, a document used during patient intake, which increased screening of TSE from 46% to 85%. Creating an educational handout in our electronic record addressing TSE increased TSE reduction counseling from 44% to 80% of children with smokers in the home. Conclusions: Incorporating TSE screening into established nursing documentation of vital signs led to the sustained screening of TSE among children in a pediatric pulmonology practice. Embedding educational material in our electronic record and changes in clinic processes increased TSE reduction counseling. Similar changes could improve rates of counseling caregivers of other guidelines aimed to improve the children's health.

Inhibition of diverse opportunistic viruses by structurally optimized retrograde trafficking inhibitors.

Opportunistic viruses are a major problem for immunosuppressed individuals, particularly following organ or stem cell transplantation. Current treatments are non-existent or suffer from problems such as high toxicity or development of resistant strains. We previously published that a trafficking inhibitor that targets a host protein greatly reduces the replication of human cytomegalovirus. This inhibitor was also shown to be moderately effective against polyomaviruses, another family of opportunistic viruses. We have developed a panel of analogues for this inhibitor and have shown that these analogues maintain their high efficacy against HCMV, while substantially lowering the concentration required to inhibit polyomavirus replication. By targeting a host protein these compounds are able to inhibit the replication of two very different viruses. These observations open up the possibility of pan-viral inhibitors for immunosuppressed individuals that are effective against multiple, diverse opportunistic viruses.

Major publications in the critical care pharmacotherapy literature: January-December 2016.

PURPOSE: To summarize select critical care pharmacotherapy guidelines and studies published in 2016. SUMMARY: The Critical Care Pharmacotherapy Literature Update (CCPLU) Group screened 31 journals monthly for relevant pharmacotherapy articles and selected 107 articles for review over the course of 2016. Of those included in the monthly CCPLU, three guidelines and seven primary literature studies are reviewed here. The guideline updates included are as follows: hospital-acquired pneumonia and ventilator-associated pneumonia management, sustained neuromuscular blocking agent use, and reversal of antithrombotics in intracranial hemorrhage (ICH). The primary literature summaries evaluate the following: dexmedetomidine for delirium prevention in post-cardiac surgery, dexmedetomidine for delirium management in mechanically ventilated patients, high-dose epoetin alfa after out-of-hospital cardiac arrest, ideal blood pressure targets in ICH, hydrocortisone in severe sepsis, procalcitonin-guided antibiotic de-escalation, and empiric micafungin therapy. CONCLUSION: The review provides a synopsis of select pharmacotherapy publications in 2016 applicable to clinical practice.

A Case of Severe, Refractory Hypotension After Amlodipine Overdose.

Calcium channel blockers (CCBs) are responsible for a substantial portion of the mortality associated with cardiovascular medication overdose cases. Amlodipine, a dihydropyridine CCB, can cause prolonged hypotension in overdose. This report describes a severe amlodipine overdose case that was refractory to multiple therapeutic approaches. A 53-year-old male presented after ingesting eighty 10 mg amlodipine tablets in a suicide attempt. The patient was initially managed with calcium boluses, glucagon, multiple vasoactive agents, lipid emulsion infusions and hyperinsulinemic euglycemic therapy. Methylene blue boluses were initiated when hypotension persisted despite conventional treatments. Refractory hypotension prompted the use of plasmapheresis in an attempt to lower serum amlodipine levels. Finally, the patient was placed on extracorporeal membrane oxygenation (ECMO) to maintain perfusion while the effects of the amlodipine ingestion dissipated. Following an episode of asystole and pulseless electrical activity prior to the start of ECMO, the patient suffered an anoxic brain injury and suspected herniation prompting the family to withdraw medical care. There is limited evidence in the literature describing the refractory treatment modalities utilized in this patient. This report is unique as it describes the clinical course of a patient when a multitude of unique treatments were combined.

Potent Inhibition of Human Cytomegalovirus by Modulation of Cellular SNARE Syntaxin 5.

Formation of the cytoplasmic viral assembly compartment (cVAC) is an important step for efficient human cytomegalovirus (HCMV) assembly. To do this, the virus must alter and repurpose the normal cellular balance of membrane and protein flux, a process that is not well understood. Although a recent screen identified three viral proteins essential for cVAC formation, less is known about the contribution of cellular factors. We show that HCMV infection increases the protein level of a cellular trafficking factor, syntaxin 5 (STX5), a member of the syntaxin family of SNARE proteins. STX5 is recruited to the cVAC in infected cells and is required for the efficient production of infectious virions. We find that STX5 is important for normal cVAC morphology and the proper localization of viral proteins. A previously identified inhibitor of trafficking, Retro94, causes the mislocalization of STX5, an altered cVAC morphology, and dispersal of viral proteins. The presence of Retro94 results in severely impaired production of infectious virions, with a decrease as great as 5 logs. We show that this inhibition is conserved among different strains of HCMV and the various cell types that support infection, as well as for murine CMV. Thus, our data identify a key cellular trafficking factor important for supporting HCMV infection. IMPORTANCE: Human cytomegalovirus (HCMV) infection causes severe disease and mortality in immunocompromised individuals, including organ transplant and AIDS patients. In addition, infection of a developing fetus may result in lifelong complications such as deafness and learning disabilities. Understanding in detail the processes involved in HCMV replication is important for developing novel treatments. One of these essential processes, assembly of infectious virions, takes places in the cytoplasmic viral assembly compartment. We identify a cellular protein, syntaxin 5, important for generating this compartment, and show that it is required for the efficient production of infectious virions. We also show that a small molecule that disrupts this protein also significantly reduces the amount of infectious virions that are generated. Thus, by pinpointing a cellular protein that is important in the replication cycle of HCMV, we identified a novel target that can be pursued for therapeutic intervention.

Mesenteric infarction due to iatrogenic polycythemia.

BACKGROUND: Polycythemia vera is defined as a chronic myeloproliferative disorder characterized by increased red blood cell count. There have been no reports on mesenteric thrombosis resulting from iatrogenic polycythemia. METHODS: We present a patient with a history of non-small cell lung cancer undergoing maintenance oral chemotherapy on tarceva and adjunctive use of procrit. The patient presented to our emergency department with an acute abdomen and was found to have ischemic bowel from unmonitored procrit, which lead to hyperviscosity of blood and mesenteric infarction. RESULTS: The patient remained intubated with ventilator support. He refused a tracheostomy. He continued on feeding through the J port of the nasojejunal tube. His white cell count, and hematocrit and creatinine levels remained normal. Procrit use and chemotherapy were not restarted. He was transferred to a subacute nursing facility for further treatment. CONCLUSIONS: Procrit and other erythropoiesis stimulating drugs can cause significant morbidity and mortality with an increased risk of cardiovascular events, gastrointestinal bleeding, thromboembolism and stroke. This case report suggests that without closely monitoring hematocrit levels, epoetin may also be associated with an increased risk of mesenteric infarction.

Mesenteric infarction due to iatrogenic polycythemia / 世界急诊医学杂志（英文）

BACKGROUND:Polycythemia vera is defined as a chronic myeloproliferative disorder characterized by increased red blood cell count. There have been no reports on mesenteric thrombosis resulting from iatrogenic polycythemia.METHODS:We present a patient with a history of non-small cell lung cancer undergoing maintenance oral chemotherapy on tarceva and adjunctive use of procrit. The patient presented to our emergency department with an acute abdomen and was found to have ischemic bowel from unmonitored procrit, which lead to hyperviscosity of blood and mesenteric infarction.RESULTS:The patient remained intubated with ventilator support. He refused a tracheostomy. He continued on feeding through the J port of the nasojejunal tube. His white cell count, and hematocrit and creatinine levels remained normal. Procrit use and chemotherapy were not restarted. He was transferred to a subacute nursing facility for further treatment.CONCLUSIONS:Procrit and other erythropoiesis stimulating drugs can cause significant morbidity and mortality with an increased risk of cardiovascular events, gastrointestinal bleeding, thromboembolism and stroke. This case report suggests that without closely monitoring hematocrit levels, epoetin may also be associated with an increased risk of mesenteric infarction.

Large neglected ulcerated melanoma mimicking extramedullary plasmacytoma.

Amelanotic melanoma, a renowned impersonator, has taken on a new persona. A 63-year-old woman was seen in the emergency room with a chief complaint of back pain after a fall and was discovered to have a 15-cm fungating mottled gray mass independent of bone on the right elbow. Initial workup discovered lytic calvarial lesions, anemia (Hb 7; Hct 20%), and circulating plasma cells consistent with plasma cell myeloma. Biopsy of the elbow mass displayed sheets of plasmacytoid cells, some reactive for CD138. Flow cytometry revealed a substantial portion of the plasma cells in the tumor that were kappa restricted consistent with cutaneous plasmacytoma. The elbow mass was initially signed out as extramedullary involvement by her myeloma. Reevaluation of the mass after the patient experienced an explosive growth of multinodular jet black malignant melanoma on ipsilateral breast revealed MART-1 and S-100 reactivity of the majority of the cells. In retrospect, the elbow mass was a neglected primary amelanotic malignant melanoma with neoplastic plasma cells participating in its chronic inflammatory infiltrate.

The cinema of control: on diabetic excess and illness in film.

While not rare, films that represent diabetes must work around the disease's banal invisibility, and images of diabetics in film are especially susceptible to metaphor and exaggeration. This essay is the first to outline a diabetic filmography, discussing medical and cinematic strategies for visualizing the disease as well as how the illness informs family plots and heroic characters in horror films. Doing so, it participates in a larger discussion of the manner in which film images of ill or disabled groups sustain notions of "normalcy" by both representing and denying otherness.

Does a waiting room video about what to expect during an emergency department visit improve patient satisfaction?

OBJECTIVE: We created an instructional waiting room video that explained what patients should expect during their emergency department (ED) visit and sought to determine whether preparing patients using this video would 1) improve satisfaction, 2) decrease perceived waiting room times and 3) increase calls to an outpatient referral line in an ambulatory population. METHODS: This serial cross-sectional study took place over a period of 2 months before (control) and 2 months after the introduction of an educational waiting room video that described a typical patient visit to our ED. We enrolled a convenience sample of adult patients or parents of pediatric patients who were triaged to the ED waiting room; a research assistant distributed and collected the surveys as patients were being discharged after treatment. Subjects were excluded if they were admitted. The primary outcome was overall satisfaction measured on a 5-point Likert scale, and secondary outcomes included perceived waiting room time, and the number of outpatient referral-line calls. RESULTS: There were 1132 subjects surveyed: 551 prevideo and 581 postvideo. The mean age was 38 years (standard deviation [SD] 18), 61% were female and the mean ED length of stay was 5.9 hours (SD 3.6). Satisfaction scores were significantly higher postvideo, with 65% of participants ranking their visit as either "excellent" or "very good", compared with 58.1% in the prevideo group (p = 0.019); however, perceived waiting room time was not significantly different between the groups (p = 0.24). Patient calls to our specialty outpatient clinic referral line increased from 1.5 per month (95% confidence interval [CI] 0.58-2.42) to 4.5 per month (95% CI 1.19-7.18) (p = 0.032). After adjusting for possible covariates, the most significant determinants of overall satisfaction were perceived waiting room time (odds ratio [OR] 0.41, 95% CI 0.34-0.48) and having seen the ED waiting room video (OR 1.41, 95% CI 1.06-1.86). CONCLUSION: Preparing patients for their ED experience by describing the ED process of care through a waiting room video can improve ED patient satisfaction and the knowledge of outpatient clinic resources in an ambulatory population. Future studies should research the implementation of this educational intervention in a randomized fashion.

Empiric tenecteplase is associated with increased return of spontaneous circulation and short term survival in cardiac arrest patients unresponsive to standard interventions.

BACKGROUND: Prospective and retrospective studies have shown that empiric use of fibrinolytic agents in sudden cardiac arrest is safe and may improve outcomes in sudden cardiac arrest. Use of fibrinolytic agents for this indication is increasing in response to these data. METHODS: A prospective multicenter observational trial was performed in three emergency departments (EDs) to determine the proportion of patients that respond to empiric fibrinolysis with tenecteplase (TNK) after failing to respond to Advanced Cardiac Life Support (ACLS) measures. Cardiac arrest patients unresponsive to ACLS, who were given TNK by their treating physician, were enrolled in an outcome registry. Return of spontaneous circulation (ROSC), survival, complications, and neurological outcomes were recorded. RESULTS: Fifty patients received TNK after a mean of 30min of cardiac arrest and eight doses of ACLS medications. One hundred and thirteen concurrent control patients received standard ACLS measures. ROSC occurred in 26% of TNK patients (95% confidence interval (CI) 16-40%) compared to 12.4% (95% CI 6.9-20%) among ACLS controls (p=.04); 12% (4.5-24%) of TNK patients survived to admission compared to none in the control group (p=.0007); 4% (0.5-14%) survived to 24h (p=NS); and 4% (0.5-14%) survived to hospital discharge (p=NS). All survivors had a good neurological outcome (Cerebral Performance Category (CPC) 1-2). One intracranial hemorrhage (ICH) occurred. No other significant bleeding complications were observed. CONCLUSIONS: Empiric fibrinolysis with TNK in cardiac arrest is associated with increased ROSC and short term survival, and with survival to hospital discharge with good neurological function in patients who fail to respond to ACLS. Results may improve with earlier administration. Prospective controlled interventional trials are indicated to evaluate this promising new therapy.

Adenoid cystic/basal cell carcinoma of the prostate: clinicopathologic findings in 19 cases.

Adenoid cystic/basal cell carcinoma (ACBCC) of the prostate has been considered to have indolent biologic potential. However, outcome data are scant, with only one documented metastasis and death. We describe clinicopathologic features of ACBCC in 19 patients and document outcome in 15. Patients ranged in age from 43 to 83 years. All but one presented with urinary obstruction. ACBCC was diagnosed by transurethral resection in 15 cases, by needle biopsy in 3 cases, and unexpected in 1 case. Four patients had concurrent acinar adenocarcinoma. Histologically, cribriform or adenoid cystic patterns predominated in 12 cases and basal cell carcinoma pattern in 7. Five cases had prominent perineural invasion. ACBCC was immunoreactive for p63 and cytokeratins 7 and 34 beta E12 but not cytokeratin 20. After diagnosis, 5 patients underwent radical prostatectomy, 2 underwent pelvic exenteration, and the rest had no treatment. ACBCC showed extraprostatic extension in 5 cases and involved the bladder margin in 3. Metastases developed in 4 (21%) patients: liver (2), lung (2), bowel (1), and corpus cavernosum (1). In 15 cases with follow-up (0.3-11.8 years), two patients died of cancer (at 1.5 and 3 years after diagnosis), 3 remain alive with cancer, and 10 have no evidence of cancer. Thus, ACBCC of the prostate is a potentially aggressive neoplasm requiring ablative therapy.

WNT7a induces E-cadherin in lung cancer cells.

E-cadherin loss in cancer is associated with de-differentiation, invasion, and metastasis. Drosophila DE-cadherin is regulated by Wnt/beta-catenin signaling, although this has not been demonstrated in mammalian cells. We previously reported that expression of WNT7a, encoded on 3p25, was frequently downregulated in lung cancer, and that loss of E-cadherin or beta-catenin was a poor prognostic feature. Here we show that WNT7a both activates E-cadherin expression via a beta-catenin specific mechanism in lung cancer cells and is involved in a positive feedback loop. Li+, a GSK3 beta inhibitor, led to E-cadherin induction in an inositol-independent manner. Similarly, exposure to mWNT7a specifically induced free beta-catenin and E-cadherin. Among known transcriptional suppressors of E-cadherin, ZEB1 was uniquely correlated with E-cadherin loss in lung cancer cell lines, and its inhibition by RNA interference resulted in E-cadherin induction. Pharmacologic reversal of E-cadherin and WNT7a losses was achieved with Li+, histone deacetylase inhibition, or in some cases only with combined inhibitors. Our findings provide support that E-cadherin induction by WNT/beta-catenin signaling is an evolutionarily conserved pathway operative in lung cancer cells, and that loss of WNT7a expression may be important in lung cancer development or progression by its effects on E-cadherin.