Trends in Specialty Palliative Care Service Utilization and In-Hospital Outcomes for Patients With Amyotrophic Lateral Sclerosis.

Background: Hospitalized people with amyotrophic lateral sclerosis (ALS) may benefit from specialty palliative care services (sPCS). Objective: To describe access to in-hospital sPCS for people with ALS (pALS). Methods: We compared years 2010-2011 to 2018-2019, and conducted trend analyses of sPCS from 2010 to 2019 stratified by race. Results: Of 103,193 pALS admitted during the study period, 13,885 (13.4%) received sPCS. Rates of sPCS increased over time (2010-2011: 8.9% vs. 2018-2019: 16.6%; p < 0.01). From 2010 to 2019, there was an increase in sPCS (p-trend<0.01) for all studied racial groups. Conclusions: Access to palliative care has increased over time for pALS admitted to hospitals in the United States.

Clinicians' interpretation of thresholds in hospital antibiograms for gram-negative rod infections: A survey and contingent valuation study of hospitalists.

Clinical guidelines suggest that hospital antibiograms are a key component when deciding empiric therapy, but little is known about how often clinicians use antibiograms and how they influence clinicians' empiric therapy decisions. We surveyed hospitalists at seven healthcare systems in the United States on their reported practices related to antibiograms and their hypothetical prescribing for four clinical scenarios associated with gram-negative rod pathogens. Each was given a randomly assigned antibiogram susceptibility percentage, and we used contingent valuation analysis to assess whether the antibiogram susceptibility percentage was associated with prescribing practices. Of the 193 survey responders, only 52 (26.9%) respondents reported using antibiograms more than monthly. Across all four clinical scenarios, there was no evidence that antibiogram susceptibility levels influenced antibiotic prescribing practices. With limited utilization and no evidence that they influenced practice, antibiograms may have a limited role in hospitalist care delivery for common gram-negative rod infections.

Prevalence of Workplace Violence and Effects of De-escalation Training Among Hospitalists: A Pilot Study.

Introduction: Workplace violence (WPV) is increasing in healthcare and negatively impacts healthcare worker outcomes. De-escalation training for healthcare workers is recommended to reduce WPV from patients and visitors. Hospitalists may be at high risk for WPV, but the magnitude of WPV and the impact of de-escalation training among hospitalists is not known. Methods: We investigated the baseline prevalence of WPV experienced by 37 hospitalists at a single center. After an in-person de-escalation training, we measured hospitalists' self-reported "Confidence in Coping with Patient Aggression" using a validated scale (score range 10-110). Results: In the 12 months before de-escalation training, 86.5% of participants reported at least one form of WPV: 83.8% verbal abuse, 29.7% racial abuse, 18.9% physical violence, and 16.2% sexual abuse. The mean confidence score increased significantly from pre-training (43.2) to immediately after training (68.5) and remained significantly elevated at three months (57.2), six months (60.2), and after 12 months (59.9) (all P < 0.05; Ptrend <0.05). Conclusion: Hospitalists are at high risk for WPV. Structured in-person de-escalation training may provide the sustained ability for hospitalists to cope with WPV.

High-Resolution Transcriptomic Landscape of the Human Submandibular Gland.

Saliva-secreting and transporting cells are part of the complex cellular milieu of the human salivary gland, where they play important roles in normal glandular physiology and diseased states. However, comprehensive molecular characterization, particularly at single-cell resolution, is still incomplete, in part due to difficulty in procuring normal human tissues. Here, we perform an in-depth analysis of male and female adult human submandibular gland (SMG) samples by bulk RNA sequencing (RNA-seq) and examine the molecular underpinnings of the heterogeneous cell populations by single-cell (sc) RNA-seq. Our results from scRNA-seq highlight the remarkable diversity of clusters of epithelial and nonepithelial cells that reside in the SMG that is also faithfully recapitulated by deconvolution of the bulk-RNA data sets. Our analyses reveal complex transcriptomic heterogeneity within both the ductal and acinar subpopulations and identify atypical SMG cell types, such as mucoacinar cells that are unique to humans and ionocytes that have been recently described in the mouse. We use CellChat to explore ligand-receptor interactome predictions that likely mediate crucial cell-cell communications between the various cell clusters. Finally, we apply a trajectory inference method to investigate specific cellular branching points and topology that offers insights into the dynamic and complex differentiation process of the adult SMG. The data sets and the analyses herein comprise an extensive wealth of high-resolution information and a valuable resource for a deeper mechanistic understanding of human SMG biology and pathophysiology.

Genetic Study of Elf5 and Ehf in the Mouse Salivary Gland.

Salivary gland (SG) development, maturation, and homeostasis require coordinated roles of transcription factors (TFs) that dictate specific cell identities and fate. The ETS family of proteins are important transcriptional drivers of diverse cell lineages, tissue development, and differentiation programs and hence are also likely to play an important role in the SG. Here we have leveraged genomic and epigenomic data of the SG to examine the expression profile of ETS genes and identified 2 closely related paralogs, Elf5 and Ehf, that are highly expressed in distinct epithelial subpopulations. By using a well-defined mouse knockout model of Elf5, we show that Elf5, despite its enriched expression in the acinar cells, is functionally dispensable for maintaining the homeostatic state of the adult SG epithelium. The lack of a discernible phenotype of the Elf5-null SG might be due to possible functional redundancy with Ehf or other ETS factors. To probe this possibility and to examine the specific consequences of Ehf loss in the SG, we used CRISPR-Cas9 to generate mice in which the DNA-binding ETS domain of Ehf is disrupted due to an insertion mutation. We demonstrate that the Ehf mutant (EhfMut) mice exhibit a distinct cellular phenotype with decreased granular convoluted tubules that are accompanied by an increased accumulation of the intercalated Sox9-positive ductal cell population. Interestingly, the ductal phenotype of the EhfMut animals is highly pronounced in males, reaffirming the established sexual dimorphism of the SG that exists in rodents. Our results show that unlike Elf5, Ehf plays a nonredundant role in directing ductal cell differentiation of the SG and highlights the phenotypic subtlety in mutant mice of closely related TFs and the importance of careful consideration of cell type-specific studies.

A Global Vista of the Epigenomic State of the Mouse Submandibular Gland.

The parotid, submandibular, and sublingual glands represent a trio of oral secretory glands whose primary function is to produce saliva, facilitate digestion of food, provide protection against microbes, and maintain oral health. While recent studies have begun to shed light on the global gene expression patterns and profiles of salivary glands, particularly those of mice, relatively little is known about the location and identity of transcriptional control elements. Here we have established the epigenomic landscape of the mouse submandibular salivary gland (SMG) by performing chromatin immunoprecipitation sequencing experiments for 4 key histone marks. Our analysis of the comprehensive SMG data sets and comparisons with those from other adult organs have identified critical enhancers and super-enhancers of the mouse SMG. By further integrating these findings with complementary RNA-sequencing based gene expression data, we have unearthed a number of molecular regulators such as members of the Fox family of transcription factors that are enriched and likely to be functionally relevant for SMG biology. Overall, our studies provide a powerful atlas of cis-regulatory elements that can be leveraged for better understanding the transcriptional control mechanisms of the mouse SMG, discovery of novel genetic switches, and modulating tissue-specific gene expression in a targeted fashion.

Erythropoietin Ameliorates Lung Injury by Accelerating Pulmonary Endothelium Cell Proliferation via Janus Kinase-Signal Transducer and Activator of Transcription 3 Pathway After Kidney Ischemia and Reperfusion Injury.

BACKGROUND/AIMS: Kidney ischemia and reperfusion injury could cause microvascular barrier dysfunction, lung inflammatory cascades activation, and programmed cell death of pulmonary endothelium, leading to acute lung injury. Our study aimed at determining whether erythropoietin (EPO) can ameliorate lung dysfunction following renal ischemia and reperfusion (IR) injury and explored the underlying mechanisms. METHODS: In vivo, C57BL/6 mice received EPO (6000 U/kg) before right renal vascular pedicles clamping for 30 minutes, followed by 24 hours of reperfusion. The lung histopathologic changes and inflammatory cytokines expression were assessed. In vitro, cultured human umbilical vein endothelial cells were treated with EPO, and apoptosis rate, proliferation capacity, and phosphorylation status of the Janus kinase-signal transducer and activator of transcription 3 (Jak-STAT3) pathway were measured respectively in the presence or absence of lipopolysaccharide stimulation. RESULTS: In vivo, EPO remarkably attenuated pulmonary interstitial and alveolar epithelial edema caused by renal IR injury. In vitro, the proliferation capacity of human umbilical vein endothelial cells was significantly increased under EPO stimulation, which correlated with changes in Jak-STAT3 signaling. CONCLUSION: Our data indicated that EPO is able to ameliorate acute lung tissue damage induced by renal IR, and at least in part, via the Jak-STAT3 pathway.

Linking care of patients with obesity to outpatient weight control clinics following acute hospitalizations.

Despite obesity impacting over one-third of US adults, guideline recommendations have not been effectively utilized by health care providers in hospital settings. Initiation of weight loss plans for obese patients during hospitalizations followed by linkage of care to weight control centers may improve compliance with the guidelines. Provider recognition and awareness that obesity is a chronic condition that warrants inpatient counsel and management with appropriate arrangement of postdischarge follow-up care will be critical to guideline implementation.

Comment to: What are the problems, information needs and objectives of community pharmacists? A mixed method approach

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[The role of Tim-3 mRNA in acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: To investigate the role of Tim-3 gene expression in acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Patients after allo-HSCT were retrospectively analyzed, this cohort of patients were divided into different groups according to disease states (grade 0-Ⅰ aGVHD group, grade Ⅱ-Ⅳ aGVHD group, improved aGVHD group) and time periods (+14-+30 d, +31-+60 d, +61-+100 d) to compare PBMC Tim-3 mRNA expression and plasma IFN-γ, IL-2 concentrations among them. RESULTS: RT-PCR showed that in grade 0-Ⅰ aGVHD group, Tim-3 mRNA expression in patients +31-+60 d (7.24±2.79) was significantly higher than that in patients + 14-+ 30 d (4.60±1.66) and + 61-+ 100 d (3.86±1.36) (P<0.05). Tim-3 mRNA expressions of grade Ⅱ-Ⅳ aGVHD group in patients +14-+30 d, +31-+60 d, +61-+100 d were 9.54± 3.05, 10.14±3.28, 12.82±4.20, respectively, which in both +14-+30 d and +61-+100 d were significantly higher than that of grade 0-Ⅰ aGVHD and improved aGVHD groups (P<0.05). In patients +31-+60 d, Tim-3 expression of grade Ⅱ-Ⅳ aGVHD group was higher than improved aGVHD group (2.49±0.89), while no statistical difference when compared with grade 0-Ⅰ aGVHD group (7.24±2.79). In grade Ⅱ-Ⅳ aGVHD group, Tim-3 mRNA expression manifested no statistical difference among grades or organ involved (P>0.05). ELISA results showed that plasma IFN-γ and IL-2 concentrations were higher in grade Ⅱ-Ⅳ aGVHD group than of other groups, while no significant difference existed between grade 0-Ⅰ aGVHD and improved aGVHD groups (P<0.05). CONCLUSION: Tim-3 played an important role in the process of aGVHD.

Prevalence of dysphagia in patients with head and neck cancer at dental clinic, Hospital USM

Prevalence of dysphagia is one of the important epidemiological data which will contribute to the proper planning and support the setting up of a swallowing rehabilitation clinic at this hospital. The present study aimed to determine the prevalence of dysphagia in patients with head and neck cancer (HNC) at Hospital Universiti Sains Malaysia (Hospital USM) from 2001-2010. In this institutional retrospective study, a total of 66 records were obtained comprising of 86.4% Malay patients, 9.1% Chinese, 1.5% Indians, and 3% other ethnic groups. These data were taken from the database of HNC patients seen at the dental clinic, Hospital USM between 2001 and 2010. Difficulty swallowing, frequent coughing during meal, choking, diet modification, and non-oral nutritional support were identified as signs and symptoms associated with dysphagia. Results showed that 59.1% of patients have had dysphagia before, during, or after the treatment of HNC. Data from the present study would be instrumental in increasing awareness among clinicians involved in patient care and it may help in planning the outline of management of dysphagia. Furthermore, it is anticipated to have implications for further research in swallowing and dysphagia.

Expression of GALNT2 in human extravillous trophoblasts and its suppressive role in trophoblast invasion.

Extravillus trophoblast (EVT) invasion plays a critical role in placental development. Integrins bind to extracellular matrix (ECM) proteins to mediate EVT cell adhesion, migration, and invasion. Changes in O-glycans on ß1-integrin have been found to regulate cancer cell behavior. We hypothesize that O-glycosyltransferases can regulate EVT invasion through modulating the glycosylation and function of ß1-integrin. Here, we found that the GALNT1 and GALNT2 mRNA were highly expressed in HTR8/SVneo and first trimester EVT cells. Immunohistochemstry and immunofluorescence staining showed that GALNT2 was expressed in subpopulations of EVT cells in deciduas, but not in syncytiotrophoblasts and cytotrophoblasts of placental villi. The percentage of GALNT2-positive EVT cells increased with gestational ages. Overexpression of GALNT2 in HTR8/SVneo cells significantly enhanced cell-collagen IV adhesion, but suppressed cell migration and invasion. Notably, we found that GALNT2 increased the expression of Tn antigen (GalNAc-Ser/Thr) on ß1-integrin as revealed by Vicia Villosa agglutinin (VVA) binding. Furthermore, GALNT2 suppressed the phosphorylation of focal adhesion kinase (FAK), a crucial downstream signaling molecule of ß1-integrin. Our findings suggest that GALNT2 is a critical initiating enzyme of O-glycosylation for regulating EVT invasion.

Strong impact of acute kidney injury on survival after liver transplantation.

Acute kidney injury (AKI) is a major complication in orthotopic liver transplantation (OLT). In an evaluation of Acute Kidney Injury Network (AKIN) criteria in liver transplanted patients, we retrospectively analyzed the usefulness of these criteria to predict survival of 193 consecutive patients at a single center who underwent primary OLT for clinical parameters and peak AKI. Postoperative AKI according to AKIN occurred in 60.1% of the patients, namely, stages 1, 2, and 3 in 30%, 13% and 17.1% respectively. Using multivariate logistic regression, AKIN stage 1 and 2 AKI were independently associated with the pre-OLT Model for End-Stage Liver Disease (MELD) score and age, while stage 3 AKI was independently associated with MELD and Acute Physiology and Chronic Health Evaluation (APACHE) II scores. The 28-day and 1-year mortality post-OLT of AKI patients were 15.5% and 25.9% respectively compared with 0% and 3.9% among non-AKI patients (P < .05 for both). The survival rates of non-AKI and stages 1, 2, and 3 AKI subjects were 96%, 85.5%, 84%, and 45.3%, respectively. Cox regression analysis showed independent risk factors for mortality during the first year after transplantation to include post-OLT AKI (12.1; P < .05), post-OLT infection (HR 4.7; P < .01), pre-OLT hypertension (HR 4.4; P < .01) hazard ratio [HR] and post-OLT APACHE II ≥10 (HR 3.6; P < .05). We concluded that AKI as defined by the AKIN criteria is a major complication of OLT linked to a poor outcomes. It remains to be evaluated whether aggressive perioperative therapy to prevent AKI can improve survival among OLT patients.

Lemierre's syndrome resulting from streptococcal induced otitis media and mastoiditis: a case report.

INTRODUCTION: Lemierre's syndrome is an extremely rare and almost universally fatal disease characterized as thrombophlebitis of the internal jugular venous system with subsequent metastatic infection. Fusobacterium necrophorum is the most common organism implicated in causation of Lemierre's syndrome. Group A Streptococcus has mainly been observed as a polymicrobial organism in the syndrome. We report a rare finding of a rare disease where Group A Streptococcus was the sole organism triggering Lemierre's syndrome. To our knowledge, this is only the third recorded patient with such an occurrence. CASE PRESENTATION: We describe a 9-year-old African American boy, who presented with otitis media and mastoiditis that culminated in Lemierre's syndrome. Isolates bore only Group A Streptococcus. The patient was appropriately treated and responded with full recovery from the syndrome. CONCLUSION: Since Lemierre's syndrome is classically detected by clinical diagnosis, these findings should prompt clinicians to consider Group A Streptococcus as an alternative catalyst. It should be pondered that patients who present with typical Group A streptococcal infections have the possibility for developing Lemierre's syndrome. Though this complication appears to be rare, early diagnosis and prompt intervention have proven critical in survival outcome. Indeed, what would seem to be a routine case of strep throat or otitis media easily treated with antibiotics could end up being an unalterable progression to death unless Lemierre's syndrome is immediately diagnosed and treated.

The role of landscape-dependent disturbance and dispersal in metapopulation persistence.

The fundamental processes that influence metapopulation dynamics (extinction and recolonization) will often depend on landscape structure. Disturbances that increase patch extinction rates will frequently be landscape dependent such that they are spatially aggregated and have an increased likelihood of occurring in some areas. Similarly, landscape structure can influence organism movement, producing asymmetric dispersal between patches. Using a stochastic, spatially explicit model, we examine how landscape-dependent correlations between dispersal and disturbance rates influence metapopulation dynamics. Habitat patches that are situated in areas where the likelihood of disturbance is low will experience lower extinction rates and will function as partial refuges. We discovered that the presence of partial refuges increases metapopulation viability and that the value of partial refuges was contingent on whether dispersal was also landscape dependent. Somewhat counterintuitively, metapopulation viability was reduced when individuals had a preponderance to disperse away from refuges and was highest when there was biased dispersal toward refuges. Our work demonstrates that landscape structure needs to be incorporated into metapopulation models when there is either empirical data or ecological rationale for extinction and/or dispersal rates being landscape dependent.

The p38 mitogen-activated protein kinase pathway plays a critical role in PAR2-induced endothelial IL-8 production and leukocyte adhesion.

A member of a new subfamily of G protein-coupled receptors, protease-activated receptor 2 (PAR2), is highly expressed on endothelial cells and plays an important role in inflammation. The purpose of this study was to determine the molecular mechanism used by PAR2 to induce IL-8 production and thereby mediate cell adhesion. We observed that PAR2-activating peptide (PAR2-AP) significantly increase peripheral blood mononuclear cells adhere to endothelial cells. Both PAR2-AP and the endogenous PAR2 activator trypsin caused concentration- and time-dependent increase in endothelial IL-8 production, and this effect was concentration dependently and selectively attenuated by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. Western blotting analysis showed that PAR2-AP induced phosphorylation of p38 MAPK and its upstream protein kinase MAPK kinase 3/6 (MKK3/6) in a time-dependent manner. Using reverse-transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, PAR2-AP was found to cause an increase in IL-8 mRNA expression and its transcription factor activating transcription factor 2, respectively,. As expected, these signals were suppressed by SB203580 in a concentration-dependent manner. Furthermore, introduction of dominant-negative vectors targeting p38 MAPK, MKK3, and MKK6 abolished PAR2-AP-mediated IL-8 production and cell adhesion function. In conclusion, PAR2 via p38 MAPK signaling regulates IL-8 production and thereby mediates cell adhesion.

Incorporation of Co(II) in dealuminated BEA zeolite at lattice tetrahedral sites evidenced by XRD, FTIR, diffuse reflectance UV-Vis, EPR, and TPR.

A CoSiBEA zeolite is prepared by a two-step postsynthesis method that consists of first creating vacant T-sites with associated silanol groups by dealumination of TEABEA zeolite with nitric acid and then impregnating the resulting SiBEA zeolite with an aqueous solution of Co(NO3)2. The incorporation of Co into lattice sites of SiBEA is evidenced by XRD. The consumption of OH groups is monitored by FTIR. The presence of Co in its II oxidation state and in tetrahedral coordination is evidenced by diffuse reflectance UV-vis and EPR spectroscopy. The very high reduction temperature (1120 K) of cobalt in CoSiBEA zeolite determined by TPR confirms that Co interacts strongly with the zeolite support, consistent with lattice tetrahedral (T(d)) coordination.

Influence of V content on the nature and strength of acidic sites in VSibeta zeolite evidenced by IR spectroscopy.

VSibeta zeolites prepared by a two-step postsynthesis method have been characterized by physical techniques. A significant reduction of intensity of the IR band near 3515 cm(-1) after impregnation of dealuminated beta zeolite with aqueous NH4VO3 indicates that V ions specifically react with hydrogen-bonded SiO-H groups of vacant T sites. IR bands at 3618 and 3645 cm(-1) are assigned to SiO-H groups interacting with V and to VO-H groups, respectively. In VSibeta, diffuse reflectance UV-visible data show that below 1.9 wt % V is present as lattice tetrahedral species and at higher content as extra-lattice octahedral species (mononuclear and polynuclear). VSibeta samples are EPR-silent at 298 or 77 K suggesting that there are no paramagnetic VIV ions. IR studies show that V-OH groups are less acidic than Si-OH-Al groups of parent HAlbeta zeolite. IR results of CO adsorption evidence three kinds of Lewis acidic sites, related to lattice mononuclear and extra-lattice mononuclear and polynuclear V species. Quantitative IR studies of ammonia and pyridine adsorption reveal that only about half of V introduced into zeolite is able to form either Brønsted or Lewis acidic sites.

Outcomes of a disease-management program for patients with recent osteoporotic fracture.

INTRODUCTION: The purpose of this study was to evaluate outcomes of a disease-management program designed to increase rates of bone-mineral-density (BMD) testing and initiation of osteoporosis medication among patients with a recent osteoporotic fracture. STUDY DESIGN: We identified 744 consecutive patients aged>or=55 years who were seen at either of 2 of 14 Kaiser Permanente medical facilities in Northern California (KPNC) after sustaining a fracture of the hip, spine, wrist, or humerus between April 2003 and May 2004. These patients were invited to participate in a study of the Fragile Fracture Management Program, whose protocol used fracture-risk assessment tools to determine treatment recommendations. Postfracture care of study participants was compared with usual postfracture care received by osteoporotic-fracture patients at 12 other KPNC facilities. RESULTS: Of the 744 patients who were invited to participate in the study, 293 (39%) agreed to participate, and 169 (23%) completed the evaluation. Of these 169 patients (127 women, 42 men), 65 (51%) of the women and 7 (17%) of the men qualified for drug treatment; of these 72 patients, 6 (86%) of the men and 41 (63%) of the women accepted the offered treatment. At the two study locations, rates of care (BMD testing or prescribing osteoporosis medication) were about twice as high as rates of usual postfracture care observed at 12 other medical centers in KPNC. CONCLUSIONS: Compared with patients who received usual care for osteoporotic fracture, patients participating in a postfracture disease management program had substantially higher rates of medical attention given for osteoporosis; however, the overall yield of the program was low. This low uptake rate was related to factors not previously appreciated: many patients refused participation in the program; a high proportion of younger women-and men of all ages-did not qualify for treatment; and treatment was refused by one in three study-qualified women and by one in seven study-qualified men. Additional efforts are needed to overcome patient barriers to improved osteoporosis evaluation, treatment and participation in postfracture programs.