Development of an inhaled endotoxin challenge protocol for characterizing evoked cell surface phenotype and genomic responses of airway cells in allergic individuals.

BACKGROUND: Environmental exposure to endotoxin is a known cause of exacerbation of asthma. Inhaled endotoxin protocols have been used to evaluate airway cell surface phenotypes associated with antigen presentation and innate immunity in healthy volunteers, but not in allergic volunteers. OBJECTIVES: To establish the safety of challenge with low-dose endotoxin (10,000 endotoxin units) (lipopolysaccharide [LPS]) inhalation in allergic individuals, to measure airway cell surface phenotypes associated with antigen presentation and innate immunity in induced sputum (IS) after LPS challenge, and to conduct gene expression profiling in IS cells to determine which host genetic networks are modified by LPS inhalation. METHODS: Induced sputum was obtained before and 6 hours after LPS inhalation in 10 allergic volunteers (8 with asthma and 2 with rhinitis). Flow cytometry was used to examine cell surface phenotypes on IS cells. Genomic expression was analyzed on a subset of IS samples (n = 10) using microarray and ingenuity pathway analysis. RESULTS: A total of 10,000 endotoxin units of LPS induced significant up-regulation of membrane CD14, CD11b, CD16, HLA-DR, CD86, and Fcepsilon receptor 1 on sputum phagocytes and increased expression of genes that influence antigen-presenting surface molecules (HLA-DR, chemokine ligand 2 or monocyte chemoattractant protein 1, v-rel reticuloendotheliosis viral oncogene homolog, prostaglandin-endoperoxide synthase 2 or cyclooxygenase 2, and transforming growth factor beta), immune activation (CD14, interleukin 1beta, and regulated upon activation, normal T cell expressed and secreted), and inflammation (intracellular adhesion molecule 1 and inhibitory kappaBalpha). Gene profiles for nuclear factor kappaB, interleukin 1, and tumor necrosis factor pathways were also significantly affected. CONCLUSIONS: Low-dose inhaled endotoxin challenge is safe in allergic individuals with mild to moderate disease. It enhances airway cell surface phenotypes and expression of genes associated with antigen presentation, innate immunity, and inflammation. Microarray with ingenuity pathway analysis can be successfully applied to sputum cells to characterize genetic responses to inhaled exacerbants.     

Fish Hydrolysate Supplementation Containing n-3 Long Chain Polyunsaturated Fatty Acids and Peptides Prevents LPS-Induced Neuroinflammation

Neuroinflammation constitutes a normal part of the brain immune response orchestrated by microglial cells. However, a sustained and uncontrolled production of proinflammatory factors together with microglial activation contribute to the onset of a chronic low-grade inflammation, leading to neuronal damage and cognitive as well as behavioral impairments. Hence, limiting brain inflammatory response and improving the resolution of inflammation could be particularly of interest to prevent these alterations. Dietary n-3 long chain polyunsaturated fatty acids (LC-PUFAs) and low molecular weight peptides are good candidates because of their immunomodulatory and proresolutive properties. These compounds are present in a fish hydrolysate derived from marine-derived byproducts. In this study, we compared the effect of an 18-day supplementation with this fish hydrolysate to a supplementation with docosahexaenoic acid (DHA) on lipopolysaccharide (LPS)-induced inflammation in mice. In response to peripherally injected LPS, the fish hydrolysate supplementation decreased the hippocampal mRNA expression of the proinflammatory cytokines IL-6 (p < 0.001), IL-1β (p = 0.0008) and TNF-α (p < 0.0001), whereas the DHA supplementation reduced only the expression of IL-6 (p = 0.004). This decline in proinflammatory cytokine expressions was associated with an increase in the protein expression of IκB (p = 0.014 and p = 0.0054 as compared to the DHA supplementation and control groups, respectively) and to a modulation of microglial activation markers in the hippocampus. The beneficial effects of the fish hydrolysate could be due in part to the switch of the hippocampal oxylipin profile towards a more anti-inflammatory profile as compared to the DHA supplementation. Thus, the valorization of fish byproducts seems very attractive to prevent and counteract neuroinflammation.     

Rapid,Full-Scale Change to Virtual PCIT During the COVID-19 Pandemic: Implementation and Clinical Implications

Health agencies call for the immediate mobilization of existing interventions in response to numerous child and family mental health concerns that have arisen as result of the COVID-19 pandemic. Answering this call, this pilot study describes the rapid, full-scale change from a primarily clinic-based Parent–Child Interaction Therapy (PCIT) model to a virtual service model (i.e., I-PCIT) in an academic and community-based program in Miami, Florida. First, we describe the virtual service training model our program developed and its implementation with 17 therapists (M_Age?=?32.35, 88.2% female, 47.1% Hispanic) to enable our clinic to shift from providing virtual services to a small portion of the families served (29.1%) to all of the families served. Second, we examine the effect of I-PCIT on child and caregiver outcomes during the 2-month stay-at-home period between March 16, 2020, and May 16, 2020, in 86 families (M_ChildAge?=?4.75, 71% Hispanic). Due to the rapid nature of the current study, all active participants were transferred to virtual services, and therefore there was no comparison or control group, and outcomes represent the most recently available scores and not treatment completion. Results reveal that I-PCIT reduced child externalizing and internalizing problems and caregiver stress, and increased parenting skills and child compliance with medium to large effects even in the midst of the COVID-19 pandemic. Finally, the study examined components of our virtual service training model associated with the greatest improvements in child and caregiver outcomes. Preliminary findings revealed that locally and collaboratively developed strategies (e.g., online communities of practice, training videos and guides) had the strongest association with child and caregiver outcomes. Implications for virtual service delivery, implementation, and practice in the midst of the COVID-19 pandemic are discussed.

     

Management of lower urinary tract fibroepithelial polyps in children

IntroductionFibroepithelial polyps (FEP) of the lower urinary tract are relatively common in adults but rare in children, with fewer than 250 cases reported in the literature to date.ObjectiveThe aim of this study was to address the experience of FEP management in children.Study designA retrospective multicenter review was undertaken in children with defined FEP of the lower urinary tract managed between 2008 and 2018. The data at 18 pediatric surgery centers were collected. Their demographic, radiological, surgical, and pathological information were reviewed.ResultsA total of 33 children (26 boys; 7 girls) were treated for FEP of the lower urinary tract at 13 centers. The most common presentation was urinary outflow as hematuria (41%), acute urinary retention (25%), dysuria (19%), or urinary infections (28%). A prenatal diagnosis was made for three patients with hydronephrosis. Almost all of the children (94%) underwent ultrasound imaging of the urinary tract as the first diagnostic examination, 23 (70%) of them also either had an MRI (15%), cystourethrography (25%), computerized tomography (6%), or cystoscopy (45%). Two of these children (6%) had a biopsy prior to the surgery. The median preoperative delay was 7.52 (range: 1–48) months. Most of the patients were treated endoscopically, although four (12.1%) had open surgery and two (6.1%) had an additional incision for specimen extraction. The median hospital stay was 1.5 (range: 1–10) days. There were no recurrences and no complications after a median follow-up of 13 (range: 1–34) months.DiscussionThe main limitation of our study is the retrospective design, although it is the largest one for this pathology.ConclusionThis series supports sonography as the most suitable diagnosis tool before endoscopy to confirm the diagnosis and to perform the resection for most FEP in children. This report confirms the recognized benign nature in the absence of recurrences.Level of EvidenceLevel V.     

Outcomes Following Percutaneous Microwave and Cryoablation of Lung Metastases from Adenoid Cystic Carcinoma of the Head and Neck: A Bi-Institutional Retrospective Cohort Study

Annals of Surgical Oncology - The aim of this study was to report outcomes following percutaneous microwave and cryoablation of lung metastases from adenoid cystic carcinoma (ACC) of the head and...     

Creating patient-centered radiology reports to empower patients undergoing prostate magnetic resonance imaging

IntroductionAs we progress to an era when patient autonomy and shared decision-making are highly valued, there is a need to also have effective patient-centered communication tools. Radiology reports are designed for clinicians and can be very technical and difficult for patients to understand. It is important for patients to understand their magnetic resonance imaging (MRI) report in order to make an informed treatment decision with their physician. Therefore, we aimed to create a patient-centered prostate MRI report to give our patients a better understanding of their clinical condition.MethodsA prototype patient-centered radiology report (PACERR) was created by identifying items to include based on opinions sought from a group of patients undergoing prostate MRI and medical experts. Data was collected in semi-structured interviews using a salient belief question. A prototype PACERR was created in collaboration with human factors engineering and design, medical imaging, biomedical informatics, and cancer patient education groups.ResultsFifteen patients and eight experts from urology, radiation oncology, radiology, and nursing participated in this study. Patients were particularly interested to have a report with laymen terms, concise language, contextualization of values, definitions of medical terms, and next course of action. Everyone believed the report should include the risk of MRI findings actually being cancer in the subsequent biopsy.ConclusionsA prostate MRI PACERR has been developed to communicate the most important findings relevant to decision-making in prostate cancer using patient-oriented design principles. The ability of this tool to improve patient knowledge and communication will be explored.     

受体－A蛋白融合蛋白制备抗P物质受体血清及其特性

受体－Ａ蛋白融合蛋白制备抗Ｐ物质受体血清及其特性ＷａｌｔｅｒＫ．Ｋ．Ｈｏ（何国强）；ＡｌｅｘｉｓＰ．Ｋ．Ｃｈｅ，郑德枢（香港中文大学；香港生物化学系，香港沙田；广州医学院神经科学研究所，广州５１０１８２）本文报告了用直肠杆菌表达Ｐ物质受体－Ａ蛋白融合...     

Comparison of fascial and vaginal wall slings in the management of intrinsic sphincter deficiency

Objectives

To compare safety and efficacy of fascial versus vaginal wall slings in the management of women with intrinsic sphincter deficiency (ISD).

Methods

The hospital and office records of 79 consecutive women with ISD were retrospectively analyzed from January 1991 to September 1995. There were 43 fascial slings (group A) and 36 vaginal wall slings (group B). Parameter of evaluation included efficacy based on postoperative presence of stress or urge incontinence and number of pads used, complications, and miscellaneous factors, including length of catheterization time, length of hospitalization, quantity of analgesics used, and loss of work days.

Results

Baseline clinical and urodynamic data were the same for both groups. Pad use decreased from 6.9 to 0.6 for group A and from 5.7 to 0.3 for group B. Persistent stress and urge incontinence was present in 5% and 16% of group A patients and in 3% and 11 % of group B patients, respectively. Group A (89%) and group B (94%) patients were either very satisfied or satisfied with their surgical outcome. The operative time, hospital days, and days lost from work for group B patients (42.3 ± 13.4 minutes, 1.4 ± 0.9 days, 18.4 ±3.2 days, respectively) were significantly lower than for group A patients (84.2 ± 17.8 minutes, 3.7 ± 1.9 days, 28.4 ±7.8 days, respectively).

Conclusions

Both fascial and vaginal wall slings are effective in treating women with ISD. However, the use of vaginal wall slings resulted in significantly shorter hospital stay, decreased catheterization time, decreased use of analgesics, and decreased loss of days of work compared with fascial slings. Therefore, the vaginal wall sling should be the preferred surgical method of treating intrinsic sphincter deficiency.