Targeted therapy and elderly people: A review

Publication date: December 2016
Source:European Journal of Cancer, Volume 69
Author(s): Amaury Daste, Camille Chakiba, Charlotte Domblides, Marine Gross-goupil, Amandine Quivy, Alain Ravaud, Pierre Soubeyran
The use of targeted therapy (TT) has radically changed the outcome of various cancers and introduces the era of personalised medicine. Elderly patients (≥65 years) represent the majority of cancer diagnoses and deaths by age group with an increase expected over the next decade. This group of patients is heterogeneous with three categories of patients: fit, vulnerable and frail, with specific treatment for each subgroup. In this review, we assess safety and efficacy of TT in elderly patients, principally from data of pivotal clinical trials with subgroup analysis, but elderly people represented a small percentage of the total number of patients. Few specific trials have been carried out for TT in elderly people with most patients considered to be fit. However, tolerance and efficacy of TT in elderly patients seems similar to that for younger patients, with an increase in incidence of specific adverse events in elderly patients for selected TTs. An adapted geriatric selection and strict monitoring could help to decrease toxicity, and specific clinical trials for elderly cancer patients would be useful.



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Bullous pemphigoid-like reaction in a patient with metastatic melanoma receiving pembrolizumab and previously treated with ipilimumab

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The need for fundamental reforms in the pain research field to develop innovative drugs.

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The need for fundamental reforms in the pain research field to develop innovative drugs.

Expert Opin Drug Discov. 2016 Nov 14;

Authors: Nagakura Y

Abstract
INTRODUCTION: Chronic pain is a major healthcare issue owing to its high prevalence, significant physical and emotional burden on the patients, and huge financial burden on the society. The efficacy of currently available medications is unsatisfactory owing to their limited effect size and the low responder rate (less than 50%). Thus, there is a large unmet need for innovative therapies for chronic pain. Areas covered: In this review, the author points out the need for fundamental reforms in pain research. For the last several decades, drug discovery research has extensively focused on designing new therapies using animal models of chronic pain. It has, however, made insufficient progress with respect to the launch of innovative analgesic drugs, because the translation from preclinical to clinical stages has not been satisfactory. Thus, the strategies for developing innovative analgesic drugs are discussed. Expert opinion: Points to be considered in the discovery of drugs for pain relief include: (1) the exclusion of bias incorporation and the alignment of clinical and preclinical endpoints in the assessment of analgesic efficacy; (2) the understanding of primary unmet needs; (3) the assessment of new therapies by biomarker-prioritized frameworks, and (4) the stratification of chronic pain sufferers.

PMID: 27838932 [PubMed - as supplied by publisher]

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Inflammation and Oxidative Stress in Cardiac Surgery Patients Treated to Intensive vs. Conservative Glucose Targets.

Inflammation and Oxidative Stress in Cardiac Surgery Patients Treated to Intensive vs. Conservative Glucose Targets.

J Clin Endocrinol Metab. 2016 Nov 14;:jc20163197

Authors: Reyes-Umpierrez D, Davis G, Cardona S, Pasquel FJ, Peng L, Jacobs S, Vellanki P, Fayfman M, Haw S, Halkos M, Guyton RA, Thourani VH, Umpierrez GE, Cde

Abstract
OBJECTIVE: We aimed to determine (a) longitudinal changes of inflammatory and oxidative stress markers and (b) the association between markers of inflammation and perioperative complications in coronary artery bypass surgery (CABG) patients treated with intensive vs. conservative blood glucose (BG) control.
METHODS: Patients with diabetes (n = 152) and without diabetes with hyperglycemia (n = 150) were randomized to intensive (n = 151, BG: 100-140 mg/dL) or to conservative (n = 151, BG: 141-180 mg/dL) glycemic targets. Plasma cortisol, high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), thiobarbituric acid-reactive substances (TBARS) and 2'-7'-dichlorofluorescin (DCF) were measured prior to and at days 3, 5 and 30 after surgery.
RESULTS: Intensive glycemic control resulted in lower mean BG (132±14 mg/dL vs. 154±17 mg/dL, p<0.001) in the ICU. Cortisol and inflammatory markers increased significantly from baseline after the 3(rd) and 5(th) day of surgery (p<0.001), and returned to baseline levels at 1 month of follow-up. Patients with perioperative complications had higher levels of cortisol, hsCRP, IL-6 and oxidative stress markers compared to those without complications. There were no significant differences in inflammatory and oxidative stress markers between patients, with or without diabetes or complications, treated with intensive or conventional glucose targets.
CONCLUSION: We report no significant differences in circulating markers of acute inflammatory and oxidative stress response in cardiac surgery patients, with or without diabetes, treated with intensive (100-140 mg/dL) or conservative (141-180 mg/dL) insulin treatment.

PMID: 27841946 [PubMed - as supplied by publisher]

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Vascular disease is associated with the expression of genes for intestinal cholesterol transport and metabolism.

Vascular disease is associated with the expression of genes for intestinal cholesterol transport and metabolism.

J Clin Endocrinol Metab. 2016 Nov 14;:jc20162728

Authors: Widdowson WM, McGowan A, Phelan J, Boran G, Reynolds J, Gibney J

Abstract
CONTEXT: Intestinal cholesterol metabolism is important in influencing post-prandial lipoprotein concentrations, and might be important in the development of vascular disease.
OBJECTIVE: This study evaluated associations between expression of intestinal cholesterol metabolism genes, postprandial lipid metabolism, and endothelial function/early vascular disease in human subjects. Design / Patients: One hundred patients undergoing routine oesophago-gastro-duedonscopy were recruited. mRNA levels of NPC1-L1, ABC-G5, ABC-G8, ABC-A1, MTTP, and SREBP-2 were measured in duodenal biopsies using rt-qPCR. Post-prandially, serum lipid and glycaemic profiles were measured, endothelial function was assessed using fasting and post-prandial FMD and carotid IMT was measured using B-mode ultrasonography. Subjects were divided into those above and below the median value of relative expression of each gene and results compared between the groups.
RESULTS: There were no between-group differences in demographic variables or classical cardiovascular risks. For all genes, the postprandial triglyceride incremental AUC was greater (P<0.05) in the group with greater expression. Post-prandial apoB48 levels were greater (P<0.05) in groups with greater expression of NPC1L1, ABC-G8, and SREBP-2. For all genes, post-prandial but not fasting FMD was greater (P<0.01) in the group with greater expression. Triglyceride and ApoB48 levels correlated significantly with postprandial FMD. CIMT was greater (P<0.05) in groups with greater expression of MTTP, ABC-A1, and SREBP-2.
CONCLUSION: Intestinal cholesterol metabolism gene expression is significantly associated with postprandial increment in TG, intestinal Apo B48, and reduced post-prandial FMD. Some genes were also associated with increased IMT. These findings suggest a role of intestinal cholesterol metabolism in development of early vascular disease.

PMID: 27841945 [PubMed - as supplied by publisher]

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Genetic variations of circulating adiponectin levels modulate changes in appetite in response to weight-loss diets.

Genetic variations of circulating adiponectin levels modulate changes in appetite in response to weight-loss diets.

J Clin Endocrinol Metab. 2016 Nov 14;:jc20162909

Authors: Ma W, Huang T, Heianza Y, Wang T, Sun D, Tong J, Williamson DA, Bray GA, Sacks FM, Qi L

Abstract
CONTEXT: Adiponectin plays key roles in regulating appetite and food intake.
OBJECTIVE: To investigate interactions between the genetic risk score (GRS) for adiponectin levels and weight-loss diets varying in macronutrient intake on long-term changes in appetite and adiponectin levels.
DESIGN, SETTING, AND PARTICIPANTS: A GRS was calculated based on five adiponectin-associated variants in 692 overweight adults from the 2-year Preventing Overweight Using Novel Dietary Strategies trial.
MAIN OUTCOME MEASURES: Repeated measurements of plasma adiponectin levels and appetite-related traits including cravings, fullness, prospective consumption, and hunger.
RESULTS: Dietary fat showed nominally significant interactions with the adiponectin GRS on changes in appetite score and prospective consumption from baseline to 6 months (P-interaction = 0.014 and 0.017, respectively) after adjusting for age, sex, ethnicity, baseline body mass index, and baseline respective outcome values. The GRS for lower adiponectin levels was associated with a greater decrease in appetite (P < 0.001) and prospective consumption (P = 0.008) among participants consuming a high-fat diet, whereas no significant associations were observed in the low-fat group. In addition, a significant interaction was observed between the GRS and dietary fat on 6-month changes in adiponectin levels (P-interaction = 0.021). The lower GRS was associated with a greater increase in adiponectin in the low-fat group (P = 0.02), but not associated with adiponectin changes in the high-fat group (P = 0.31).
CONCLUSIONS: Our findings suggest that individuals with varying genetic architecture of circulating adiponectin may respond divergently in appetite and adiponectin levels to weight-loss diets varying in fat intake.

PMID: 27841942 [PubMed - as supplied by publisher]

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Programming of adiposity in childhood and adolescence: associations with birth weight and cord blood adipokines.

Programming of adiposity in childhood and adolescence: associations with birth weight and cord blood adipokines.

J Clin Endocrinol Metab. 2016 Nov 14;:jc20162342

Authors: Simpson J, Smith AD, Fraser A, Sattar N, Lindsay RS, Ring SM, Tilling K, Davey Smith G, Lawlor DA, Nelson SM

Abstract
CONTEXT: Exposure to maternal adiposity during pregnancy is associated with higher offspring birthweight and greater adiposity through childhood and adult life. As birthweight reflects the summation of lean and fat mass, the extent to which fat mass at birth tracks into later life is unknown.
OBJECTIVE: Determine whether fat mass at birth is associated with child and adolescent adiposity.
DESIGN, SETTING AND PARTICIPANTS: UK birth cohort with markers of neonatal fat mass; cord blood leptin, adiponectin, and birthweight and adiposity outcomes at age 9 (N=2775) and 17years (N=2138).
MAIN OUTCOMES: Offspring BMI, waist circumference, DXA-determined fat mass and obesity at age 9 and 17years.
RESULTS: Higher cord blood leptin was associated with higher z-scores of fat mass (difference in mean per 10pg/ml: 0.03SD,95%CI 0.00-0.06), waist circumference (0.04SD,95%CI 0.00-0.07), and BMI (0.04SD,95%CI 0.00-0.08), at age 9. However, by age 17 the adjusted results were attenuated to the null. Cord blood adiponectin was not associated with measures of adiposity at age 9. At age 17, cord blood adiponectin was positively associated with fat mass (0.02SD per 10μg/ml,95%CI 0.02-0.03) and waist circumference (0.04SD per 10μg/ml,95%CI 0.03-0.05). Birthweight was positively associated with waist circumference (0.03SD per 100g,95%CI 0.02-0.04) and BMI (0.02SD per 100g,95%CI 0.00-0.03), but not fat mass or odds of obesity. Cord blood leptin and adiponectin were not associated with obesity at either age.
CONCLUSIONS: Increased cord blood leptin and adiponectin, known surrogates of fetal fat mass, were weakly associated with increased fat mass in late childhood and adolescence respectively.

PMID: 27841944 [PubMed - as supplied by publisher]

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Craniovertebral junction anomalies: When is resurgery required?

Craniovertebral junction anomalies: When is resurgery required?

Neurol India. 2016 Nov-Dec;64(6):1220-1232

Authors: Sindgikar P, Das KK, Sardhara J, Bhaisora KS, Srivastava AK, Mehrotra A, Jaiswal AK, Sahu RN, Behari S

Abstract
BACKGROUND: Craniovertebral junction (CVJ) abnormalities, such as atlantoaxial dislocation (AAD) with or without basilar invagination (BI), with or without associated Chiari malformation (CM), may cause a high cervical myelopathy. Occasionally, mechanical factors such as inadequate canal decompression, torticollis, and/or scoliosis may lead to lack of improvement following the primary surgery. Furthermore, implant-related factors, requiring implant revision/removal, or the presence of surgical site infections may cause the patient to undergo resurgery.
AIMS: This study was aimed at highlighting the underlying etiopathogenesis of resurgery following the primary surgery undertaken in CVJ abnormalities.
SETTING AND DESIGN: This was a retrospective study from a tertiary care referral institute focusing on 414 operated cases of CVJ anomalies.
MATERIALS AND METHODS: The data of 55 patients who underwent resurgery included their clinicoradiological assessment and operative records. The inclusion criteria included failed primary procedure, repeat procedure for construct failure, infection at the surgical site, or wound dehiscence. Pure CM patients without bony anomalies were excluded from the study.
RESULTS: A total of 137 procedures were performed in 55/414 (13%) patients. Causes of resurgery could be divided into ventral [redo or denovo transoral decompression (TOD) or wound-related complications, n = 33, 40.2%] and dorsal causes (implant-related factors/wound infections, n = 49, 59.8%). De novo TOD was done in persisting myelopathy following posterior fusion (PF) with C1-2 distraction (n = 15,18.3%,). Redo TOD was done for residual anterior bony compression [n = 8, 9.6%, OR 0.61; [CI = 0.20-1.86]. Causes for oral wound reexplorations (n = 10, 12.2%) included velopharyngeal insufficiency, wound resuturing, oral bleeding, and cerebrospinal fluid (CSF) leak. Dorsal causes included: (A) Implant factors (n = 27, 32.7%) and (B) neck wound reexplorations (n = 22, 26.8%). Presence of subaxial spine scoliosis, torticollis, and asymmetric joints increased the incidence of reexploration. Occipitocervical fusion rather than C1-2 fusion was more prone towards construct loosening.
CONCLUSIONS: Patients undergoing distraction with PF may require transoral surgery due to persisting myelopathy, especially in the presence of torticollis, scoliosis, and symmetrical joints. Single stage TOD+PF increases the chances of implant infection due to tissue contamination, bacteremia, or transfacetal migration of microbes. Chronic/recurrent sinus is usually a harbinger of deeper infection and can be cured with implant removal.

PMID: 27841190 [PubMed - in process]

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Reply to: Psychometric properties of the Tinnitus Functional Index (TFI): Assessment in a UK research volunteer population.

Reply to: Psychometric properties of the Tinnitus Functional Index (TFI): Assessment in a UK research volunteer population.

Hear Res. 2016 Nov 11;:

Authors: Henry JA, Thielman E, Zaugg T

PMID: 27842215 [PubMed - as supplied by publisher]

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Prevalence of Hearing Loss in Teachers of Singing and Voice Students.

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Prevalence of Hearing Loss in Teachers of Singing and Voice Students.

J Voice. 2016 Nov 10;:

Authors: Isaac MJ, McBroom DH, Nguyen SA, Halstead LA

Abstract
OBJECTIVES: Singers and voice teachers are exposed to a range of noise levels during a normal working day. This study aimed to assess the hearing thresholds in a large sample of generally healthy professional voice teachers and voice students to determine the prevalence of hearing loss in this population.
STUDY DESIGN: A cross-sectional study was carried out.
METHODS: Voice teachers and vocal students had the option to volunteer for a hearing screening of six standard frequencies in a quiet room with the Shoebox audiometer (Clearwater Clinical Limited) and to fill out a brief survey. Data were analyzed for the prevalence and severity of hearing loss in teachers and students based on several parameters assessed in the surveys. All data were analyzed using Microsoft Excel (Microsoft Corp.) and SPSS Statistics Software (IBM Corp.).
RESULTS: A total of 158 participants were included: 58 self-identified as voice teachers, 106 as voice students, and 6 as both. The 6 participants who identified as both, were included in both categories for statistical purposes. Of the 158 participants, 36 had some level of hearing loss: 51.7% of voice teachers had hearing loss, and 7.5% of voice students had hearing loss. Several parameters of noise exposure were found to positively correlate with hearing loss and tinnitus (P < 0.05). Years as a voice teacher and age were both predictors of hearing loss (P < 0.05).
CONCLUSIONS: Hearing loss in a cohort of voice teachers appears to be more prevalent and severe than previously thought. There is a significant association between years teaching and hearing loss. Raising awareness in this population may prompt teachers and students to adopt strategies to protect their hearing.

PMID: 27839986 [PubMed - as supplied by publisher]

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Extracorporeal Membrane Oxygenation in Pregnant and Postpartum Women With H1N1-Related Acute Respiratory Distress Syndrome: A Systematic Review and Meta-analysis.

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Extracorporeal Membrane Oxygenation in Pregnant and Postpartum Women With H1N1-Related Acute Respiratory Distress Syndrome: A Systematic Review and Meta-analysis.

Obstet Gynecol. 2016 Feb;127(2):241-7

Authors: Saad AF, Rahman M, Maybauer DM, Fraser JF, Costantine MM, Pacheco LD, Maybauer MO

Abstract
OBJECTIVE: To assess available evidence regarding the use of extracorporeal membrane oxygenation (ECMO) in pregnant and postpartum women with acute respiratory distress syndrome (ARDS) secondary to H1N1 infection.
DATA SOURCES: Databases from MEDLINE (U.S. National Library of Medicine, 1946 to April 1, 2015), the Cochrane Library Controlled Trials Register, ClinicalTrials.gov, and Web of Science were queried for studies on ECMO in pregnant or postpartum patients with ARDS. Search terms included: "ARDS," "ECMO," "pregnant," and "postpartum."
TABULATION, INTEGRATION, AND RESULTS: All relevant references in any language were reviewed. Literature for inclusion and methodologic quality were reviewed based on the meta-analyses and systematic reviews of observational studies (Meta-analysis Of Observational Studies in Epidemiology) guidelines. Of 266 citations, five retrospective studies (39 patients) fulfilled our inclusion criteria. No randomized controlled trials were found. The pooled estimate of the survival rate among pregnant and postpartum patients who received ECMO for ARDS secondary to H1N1 was 74.6% (95% confidence interval [CI] 60.7-88.6%). Neonatal outcomes were reported in two studies and the rate of live birth was 70% (95% CI 43.7-95.2). Heterogeneity was not significant among studies (I ranged from 0% to 21%; P>.25).
CONCLUSION: The role of ECMO in pregnant and postpartum women with ARDS from H1N1 remains unclear and the benefits suggested from our review should be interpreted with caution.

PMID: 26942349 [PubMed - indexed for MEDLINE]

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Deep Sequencing Reveals Potential Antigenic Variants at Low Frequencies in Influenza A Virus-Infected Humans.

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Deep Sequencing Reveals Potential Antigenic Variants at Low Frequencies in Influenza A Virus-Infected Humans.

J Virol. 2016 Jan 06;90(7):3355-65

Authors: Dinis JM, Florek NW, Fatola OO, Moncla LH, Mutschler JP, Charlier OK, Meece JK, Belongia EA, Friedrich TC

Abstract
UNLABELLED: Influenza vaccines must be frequently reformulated to account for antigenic changes in the viral envelope protein, hemagglutinin (HA). The rapid evolution of influenza virus under immune pressure is likely enhanced by the virus's genetic diversity within a host, although antigenic change has rarely been investigated on the level of individual infected humans. We used deep sequencing to characterize the between- and within-host genetic diversity of influenza viruses in a cohort of patients that included individuals who were vaccinated and then infected in the same season. We characterized influenza HA segments from the predominant circulating influenza A subtypes during the 2012-2013 (H3N2) and 2013-2014 (pandemic H1N1; H1N1pdm) flu seasons. We found that HA consensus sequences were similar in nonvaccinated and vaccinated subjects. In both groups, purifying selection was the dominant force shaping HA genetic diversity. Interestingly, viruses from multiple individuals harbored low-frequency mutations encoding amino acid substitutions in HA antigenic sites at or near the receptor-binding domain. These mutations included two substitutions in H1N1pdm viruses, G158K and N159K, which were recently found to confer escape from virus-specific antibodies. These findings raise the possibility that influenza antigenic diversity can be generated within individual human hosts but may not become fixed in the viral population even when they would be expected to have a strong fitness advantage. Understanding constraints on influenza antigenic evolution within individual hosts may elucidate potential future pathways of antigenic evolution at the population level.
IMPORTANCE: Influenza vaccines must be frequently reformulated due to the virus's rapid evolution rate. We know that influenza viruses exist within each infected host as a "swarm" of genetically distinct viruses, but the role of this within-host diversity in the antigenic evolution of influenza has been unclear. We characterized here the genetic and potential antigenic diversity of influenza viruses infecting humans, some of whom became infected despite recent vaccination. Influenza virus between- and within-host genetic diversity was not significantly different in nonvaccinated and vaccinated humans, suggesting that vaccine-induced immunity does not exert strong selective pressure on viruses replicating in individual people. We found low-frequency mutations, below the detection threshold of traditional surveillance methods, in nonvaccinated and vaccinated humans that were recently associated with antibody escape. Interestingly, these potential antigenic variants did not reach fixation in infected people, suggesting that other evolutionary factors may be hindering their emergence in individual humans.

PMID: 26739054 [PubMed - indexed for MEDLINE]

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Perceptions of Hong Kong Chinese women toward influenza vaccination during pregnancy.

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Perceptions of Hong Kong Chinese women toward influenza vaccination during pregnancy.

Vaccine. 2016 Jan 2;34(1):33-40

Authors: Yuen CY, Dodgson JE, Tarrant M

Abstract
INTRODUCTION: Pregnant women are the highest priority group for seasonal influenza vaccination. However, their vaccination uptake remains suboptimal. The purpose of this study is to explore Hong Kong women's perceptions of the threat of influenza infection during pregnancy, the risks and benefits of influenza vaccination, and their decision-making processes.
METHODS: We used a qualitative descriptive design and recruited women who had just given births to a live infant from April to June 2011. Participants were recruited from a large teaching hospital in Hong Kong and were interviewed in the immediate postpartum period.
RESULTS: A total of 32 postpartum women were interviewed, and two had been vaccinated during pregnancy. Following thematic analysis, three themes emerged: perceived risk of influenza infection, perceived risk of influenza vaccine, and decision-making cues. Overall, participants held negative impressions about influenza vaccination during pregnancy, and they underestimated the threat of influenza to themselves and their fetus. They were also confused about the safety and efficacy of the influenza vaccine and the differences between preventive strategies and treatment for influenza. Most participants reported that their health care providers (HCPs) did not offer or recommend vaccination. Because of negative media reports about vaccination, participants were hesitant to receive the vaccine. Motivating forces for vaccine acceptance were a perceived high prevalence of circulating influenza during their pregnancy and HCP recommendations and reassurances that the vaccination was safe, effective, and beneficial for the fetus.
CONCLUSION: Vaccination promotion strategies need to focus on encouraging HCPs to take the initiative to discuss vaccination with their pregnant clients and provide accurate and unbiased information about the risks of influenza and the benefits of vaccination.

PMID: 26616554 [PubMed - indexed for MEDLINE]

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Annual influenza vaccination reduces total hospitalization in patients with chronic hepatitis B virus infection: A population-based analysis.

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Annual influenza vaccination reduces total hospitalization in patients with chronic hepatitis B virus infection: A population-based analysis.

Vaccine. 2016 Jan 2;34(1):120-7

Authors: Su FH, Huang YL, Sung FC, Su CT, Hsu WH, Chang SN, Yeh CC

Abstract
BACKGROUND: This study evaluated hospitalization and mortality in patients with chronic hepatitis B virus infection (HBV (+)) and matched comparison patients after stratifying the patients according to annual influenza vaccination (Vaccine (+)).
METHODS: Data from Taiwan's National Health Insurance program from 2000 to 2009 were used to identify HBV(+)/vaccine(+) (n=4434), HBV(+)/Vaccine(-) (n=3646), HBV(-)/Vaccine(+) (n=8868), and HBV(-)/Vaccine(-) (n=8868) cohorts. The risk of pneumonia/influenza, respiratory failure, intensive care, hospitalization, and mortality in the four cohorts was evaluated.
RESULTS: The total hospitalization rate was significantly lower in patients with chronic HBV infection who received an annual influenza vaccination than in chronic HBV-infected patients who did not receive an influenza vaccination (16.29 vs. 24.02 per 100 person-years), contributing to an adjusted hazard ratio (HR) of 0.56 (95% confidence interval (CI)=0.50-0.62). The HBV(+)/Vaccine(+) cohort also had lower risks than the HBV(+)/Vaccine(-) cohort for pneumonia and influenza (adjusted HR=0.79, 95% CI=0.67-0.92), intensive care unit admission (adjusted HR=0.33, 95% CI=0.25-0.43), and mortality (adjusted HR=0.19, 95% CI=0.15-0.24).
CONCLUSIONS: Our results suggest that annual influenza vaccination can reduce the risk of hospitalization and mortality in patients with chronic HBV infection.

PMID: 26614589 [PubMed - indexed for MEDLINE]

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Assessment of influenza vaccine effectiveness in a sentinel surveillance network 2010-13, United States.

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Assessment of influenza vaccine effectiveness in a sentinel surveillance network 2010-13, United States.

Vaccine. 2016 Jan 2;34(1):61-6

Authors: Cowling BJ, Feng S, Finelli L, Steffens A, Fowlkes A

Abstract
BACKGROUND: Influenza vaccines are now widely used to reduce the burden of annual epidemics of influenza virus infections. Influenza vaccine effectiveness (VE) is monitored annually to determine VE against each season's circulating influenza strains in different groups such as children, adults and the elderly. Few prospective surveillance programs are available to evaluate influenza VE against medically attended illness for patients of all ages in the United States.
METHODS: We conducted surveillance of patients with acute respiratory illnesses in 101 clinics across the US during three consecutive influenza seasons. We analyzed laboratory testing results for influenza virus, self-reported vaccine history, and patient characteristics, defining cases as patients who tested positive for influenza virus and controls as patients who tested negative for influenza virus. Comparison of influenza vaccination coverage among cases versus controls, adjusted for potential confounders, was used to estimate VE as one minus the adjusted odds ratio multiplied by 100%.
RESULTS: We included 10,650 patients during three influenza seasons from August 2010 through December 2013, and estimated influenza VE in children 6m-5y of age (58%; 95% CI: 49%-66%), children 6-17y (45%; 95% CI: 34%-53%), adults 18-49y (36%; 95% CI: 24%, 46%), and adults ≥50y (34%, 95% CI: 13%, 51%). VE was higher against influenza A(H1N1) compared to A(H3N2) and B.
CONCLUSIONS: Our estimates of moderate influenza VE confirm the important role of vaccination in protecting against medically attended influenza virus infection.

PMID: 26611200 [PubMed - indexed for MEDLINE]

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Immunogenicity, safety and tolerability of inactivated trivalent influenza vaccine in overweight and obese children.

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Immunogenicity, safety and tolerability of inactivated trivalent influenza vaccine in overweight and obese children.

Vaccine. 2016 Jan 2;34(1):56-60

Authors: Esposito S, Giavoli C, Trombetta C, Bianchini S, Montinaro V, Spada A, Montomoli E, Principi N

Abstract
Obesity may be a risk factor for increased hospitalization and deaths from infections due to respiratory pathogens. Additionally, obese patients appear to have impaired immunity after some vaccinations. To evaluate the immunogenicity, safety and tolerability of an inactivated trivalent influenza vaccine (TIV) in overweight and obese children, 28 overweight/obese pediatric patients and 23 healthy normal weight controls aged 3-14 years received a dose of TIV. Four weeks after vaccine administration, significantly higher seroprotection rates against the A/H1N1 strain were observed among overweight/obese children compared with normal weight controls (p<0.05). Four months after vaccination, similar or slightly higher seroconversion and seroprotection rates against the A/H1N1 and A/H3N2 strains were detected in overweight/obese than in normal weight children, whereas significantly higher rates of seroconversion and seroprotection against the B strain were found in overweight/obese patients than in normal weight controls (p<0.05 for seroconversion and seroprotection). Geometric mean titers (GMTs) and fold increase against B strains were significantly higher in overweight/obese patients than in normal weight controls 4 months after vaccine administration (p<0.01 for GMT values and p<0.05 for fold increase). The frequency of local and systemic reactions was similar between the groups, and there were no serious adverse events. The results of this study indicate that in overweight and obese children, antibody response to TIV administration is similar or slightly higher than that evidenced in normal weight subjects of similar age and this situation persists for at least 4 months after vaccine administration in the presence of a favorable safety profile.

PMID: 26608327 [PubMed - indexed for MEDLINE]

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Interventions to increase the uptake of seasonal influenza vaccination among pregnant women: A systematic review.

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Interventions to increase the uptake of seasonal influenza vaccination among pregnant women: A systematic review.

Vaccine. 2016 Jan 2;34(1):20-32

Authors: Wong VW, Lok KY, Tarrant M

Abstract
BACKGROUND: Pregnant women and their infants under 6 months of age infected with influenza have a high risk of serious morbidity and mortality. Influenza vaccine during pregnancy offers 3-for-1 benefits to pregnant women, fetuses and newborn infants. Current vaccination uptake rates during pregnancy, however, are often lower than other high-risk groups and the general population.
METHODS: We systematically reviewed evidence on the effectiveness of interventions to improve influenza vaccination coverage in pregnant women. Risk differences (RDs) were calculated from the included studies.
RESULTS: Eleven studies were included in the review, of which four were randomized controlled trials (RCTs). Three cohort studies assessed provider-focused interventions while four RCTs and one cohort study evaluated pregnant women-focused interventions. Two cohort studies and a prospective intervention study assessed the effectiveness of bundled interventions. No study solely assessed the effectiveness of interventions to enhance access to influenza vaccination. One moderate quality RCT showed that an influenza pamphlet, with or without a verbalized benefit statement, improved the vaccination rate (RD=0.26; RD=0.39). The other reviewed RCTs showed discordant results, with RDs ranging from -0.15 to 0.03. Although all observational studies significantly improved vaccination rates (RDs ranged from 0.03 to 0.44), the quality of the evidence varied.
CONCLUSIONS: There is a lack of effective interventions to increase the influenza vaccination rate in pregnant women. Based on the existing research, we recommend that clinicians provide influenza pamphlets to pregnant women with a verbalized statement about the benefits of influenza vaccine to newborns. Further high-quality RCTs are needed to develop successful maternal influenza vaccination programs. Increased clarity in reporting the content of interventions would help to improve the comparability and generalizability of the published studies.

PMID: 26602267 [PubMed - indexed for MEDLINE]

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Effectiveness of live attenuated influenza vaccine and inactivated influenza vaccine in children 2-17 years of age in 2013-2014 in the United States.

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Effectiveness of live attenuated influenza vaccine and inactivated influenza vaccine in children 2-17 years of age in 2013-2014 in the United States.

Vaccine. 2016 Jan 2;34(1):77-82

Authors: Caspard H, Gaglani M, Clipper L, Belongia EA, McLean HQ, Griffin MR, Talbot HK, Poehling KA, Peters TR, Veney N, Ambrose CS

Abstract
BACKGROUND: A postmarketing observational study was initiated to evaluate quadrivalent live attenuated influenza vaccine (LAIV) effectiveness in children aged 2-17 years in the United States.
METHODS: Children and adolescents aged 2-17 years seeking outpatient care for febrile acute respiratory illness <5 days duration were enrolled at 4 geographically diverse sites during the 2013-2014 influenza season. Nasal swabs were tested for influenza using reverse transcription polymerase chain reaction. Vaccination status was documented from medical records or immunization registries. Children who received ≥1 dose of influenza vaccine ≥14 days before study visit were considered vaccinated. Vaccine effectiveness (VE) was estimated as 100×(1-adjusted odds ratio), where the odds of interest are the odds of vaccine exposure among influenza cases and test-negative controls.
RESULTS: In total, 1033 children and adolescents were included in the analysis. Influenza was detected in 14% (145/1033) of all children, with 74% (108/145) of the influenza cases due to A/H1N1pdm09 strains, 21% (31) to influenza B, and 4% (6) to influenza H3N2. LAIV did not show significant effectiveness against A/H1N1pdm09 (VE 13% [95% CI: -55 to 51]) but was effective against B/Yamagata strains (82% [95% CI: 12-96]). Inactivated influenza vaccine was effective against A/H1N1pdm09 (74% [95% CI: 50-86]) and B/Yamagata (70% [95% CI: 18-89]).
CONCLUSIONS: LAIV provided significant protection against B/Yamagata influenza but not against A/H1N1pdm09 in children aged 2-17 years in 2013-2014, resulting in a proposed change of the 2015-2016 formulation with a new and more heat-stable A/H1N1pdm09 LAIV strain.

PMID: 26589519 [PubMed - indexed for MEDLINE]

http://ift.tt/2fV9omy

The clinical usefulness of lymphocyte:monocyte ratios in differentiating influenza from viral non-influenza-like illnesses in hospitalized adults during the 2015 influenza A (H3N2) epidemic: the uniqueness of HPIV-3 mimicking influenza A.

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The clinical usefulness of lymphocyte:monocyte ratios in differentiating influenza from viral non-influenza-like illnesses in hospitalized adults during the 2015 influenza A (H3N2) epidemic: the uniqueness of HPIV-3 mimicking influenza A.

Eur J Clin Microbiol Infect Dis. 2016 Jan;35(1):155-8

Authors: Cunha BA, Connolly JJ, Irshad N

Abstract
During influenza epidemics, influenza-like illnesses (ILIs) viruses cocirculate with influenza strains. If positive, rapid influenza diagnostic tests (RIDTs) identify influenza A/B, but false-negative RIDTs require retesting by viral polymerase chain reaction (PCR). Patient volume limits testing during influenza epidemics, and non-specific laboratory findings have been used for presumptive diagnosis pending definitive viral testing. In adults, the most useful laboratory abnormalities in influenza include relative lymphopenia, monocytosis, and thrombocytopenia. Lymphocyte:monocyte (L:M) ratios may be even more useful. L:M ratios <2 have been used as a surrogate marker for influenza, but there are no longitudinal data on L:M ratios in hospitalized adults with viral ILIs. During the 2015 influenza A (H3N2) epidemic at our hospital, we reviewed our experience with L:M ratios in 37 hospitalized adults with non-influenza viral ILIs. In hospitalized adults with non-influenza A ILIs, the L:M ratios were >2 with human metapneumovirus (hMPV), rhinoviruses/enteroviruses (R/E), and respiratory syncytial virus (RSV), but not human parainfluenza virus type 3 (HPIV-3), which had L:M ratios <2. HPIV-3, like influenza, was accompanied by L:M ratios <2, mimicking influenza A (H3N2). In influenza A admitted adults, L:M ratios <2 did not continue for >3 days, whereas with HPIV-3, L:M ratios <2 persisted for >3 days of hospitalization.

PMID: 26563893 [PubMed - indexed for MEDLINE]

http://ift.tt/2ftS6yq

Influenza vaccination in India: Challenges for universal adoption.

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Influenza vaccination in India: Challenges for universal adoption.

Vaccine. 2016 Jan 2;34(1):1-3

Authors: Koul PA, Bali NK

PMID: 26196326 [PubMed - indexed for MEDLINE]

http://ift.tt/2fVbrHh

Influenza: déjà vu all over again.

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Influenza: déjà vu all over again.

Pediatr Rev. 2015 Mar;36(3):91

Authors: Rathore M

PMID: 25733760 [PubMed - indexed for MEDLINE]

http://ift.tt/2ftIPpS

Influenza vaccination rates for hospitalised patients: a multiyear quality improvement effort.

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Influenza vaccination rates for hospitalised patients: a multiyear quality improvement effort.

BMJ Qual Saf. 2015 Mar;24(3):221-7

Authors: Cohen ES, Ogrinc G, Taylor T, Brown C, Geiling J

Abstract
BACKGROUND: Influenza vaccination is the most effective method for preventing influenza virus infection. Adult hospitalised patients form a particularly high-risk group for severe influenza given their advanced age and comorbidities. We sought to improve the influenza vaccination rates of hospitalised patients at the White River Junction Veterans Affairs Medical Center.
METHODS: The improvement effort started in 2007 when our baseline vaccination rate was about 60%. An interprofessional team analysed the influenza vaccination process for hospitalised patients. During the course of six influenza seasons, eight Plan-Do-Study-Act cycles were used including a hospital-wide flu campaign, embedded orders in the electronic medical record (EMR) to facilitate ordering vaccinations by providers, daily reminders from ward clerks and standing orders for influenza vaccination on discharge. The measure was the monthly percentage of patients discharged from the hospital with an up-to-date influenza vaccination.
RESULTS: The percentage of veterans discharged with an up-to-date influenza vaccination increased to over 80% in February 2009 and has remained high.
CONCLUSIONS: Although we are confident that our local efforts helped to improve the vaccination rate, external factors such as the 2009 H1N1 pandemic and universal vaccination may have primed our system to respond more readily to the implemented changes. Understanding all of the relevant factors that lead to vaccination uptake can be applied to future hospital influenza vaccination campaigns. In addition, our work demonstrates that an interprofessional approach is still required to apply the functionality of the EMR effectively.

PMID: 25633277 [PubMed - indexed for MEDLINE]

http://ift.tt/2ftRWXR

Factors associated with uptake of the Influenza A(H1N1)pdm09 monovalent pandemic vaccine in K-12 Public Schools, Maine 2009-2010.

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Factors associated with uptake of the Influenza A(H1N1)pdm09 monovalent pandemic vaccine in K-12 Public Schools, Maine 2009-2010.

J Public Health Manag Pract. 2015 Mar-Apr;21(2):186-95

Authors: Lorick SA, Goldberg L, Zhang F, Birkhimer N, Dube N, Dutram K, Hubley T, Tipton M, Basurto-Davila R, Graitcer S, Mills DA

Abstract
CONTEXT AND OBJECTIVE: Maine implemented a statewide pre-K through 12-school vaccination program during the 2009-2010 H1N1 influenza pandemic. The main objective of this study was to determine which school, nurse, consent form, and clinic factors were associated with school-level vaccination rates for the first dose of the 2009 H1N1 pandemic vaccine.
METHODS: In April 2010, school nurses or contacts were e-mailed electronic surveys. Generalized linear mixed regression was used to predict adjusted vaccination rates using random effects to account for correlations within school districts. Elementary and secondary (middle and high) schools were analyzed separately.
RESULTS: Of 645 schools invited to participate, 82% (n = 531) completed the survey. After excluding schools that were ineligible or could not provide outcome data, data for 256 elementary and 124 secondary public schools were analyzed and included in the multivariable analyses. The overall, unadjusted, vaccination rate was 51% for elementary schools and 45% for secondary schools. Elementary schools that had 50 or fewer students per grade, had availability of additional nursing staff, which did not require parental presence at the H1N1 clinic or disseminated consent forms by mail and backpack (compared with backpack only) had statistically significant (P < .05) higher (adjusted) vaccination rates. For secondary schools, the vaccination rate for schools with the lowest proportion of students receiving subsidized lunch (ie, highest socioeconomic status) was 58% compared with 37% (P < .001) for schools with the highest proportion receiving subsidized lunch.
CONCLUSIONS: Several factors were independently associated with vaccination rates. For elementary schools, planners should consider strategies such as providing additional nursing staff and disseminating consent forms via multiple methods. The impact of additional factors, including communication approaches and parent and student attitudes, needs to be investigated, especially for secondary schools.

PMID: 25303864 [PubMed - indexed for MEDLINE]

http://ift.tt/2fVhlYQ

Understanding pregnant women's attitudes and behavior toward influenza and pertussis vaccination.

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Understanding pregnant women's attitudes and behavior toward influenza and pertussis vaccination.

Qual Health Res. 2015 Mar;25(3):360-70

Authors: Wiley KE, Cooper SC, Wood N, Leask J

Abstract
Internationally, pregnant and postpartum women have been the focus of influenza and pertussis immunization campaigns, with differing levels of vaccine acceptance. We used semistructured interviews to explore pregnant women's perspectives on influenza vaccination during pregnancy and postpartum pertussis vaccination. Many women saw pregnancy as a busy time filled with advice on what they "should" and "should not" do to ensure the health of their fetus, and vaccinating themselves was regarded as just one of these tasks needing consideration. Women were more concerned about potential risks to their infants' health before their own. They saw influenza as a disease affecting the mother, whereas they viewed pertussis as a threat to the baby and therefore comparatively more risky. They were thus more likely to intend to vaccinate against pertussis to protect their infant. Framing of vaccination information toward protection of the baby might help increase vaccine uptake among pregnant women.

PMID: 25246330 [PubMed - indexed for MEDLINE]

http://ift.tt/2ftTZuL

Calcinosis cutis following seasonal influenza vaccination.

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Calcinosis cutis following seasonal influenza vaccination.

J Formos Med Assoc. 2015 Sep;114(9):895-6

Authors: Chiang CH, Lin MH

PMID: 24751284 [PubMed - indexed for MEDLINE]

http://ift.tt/2ftRUPJ

'One health' and development priorities in resource-constrained countries: policy lessons from avian and pandemic influenza preparedness in Zambia.

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'One health' and development priorities in resource-constrained countries: policy lessons from avian and pandemic influenza preparedness in Zambia.

Health Policy Plan. 2015 Mar;30(2):215-22

Authors: Mwacalimba KK, Green J

Abstract
'One World, One Health' has become a key rallying theme for the integration of public health and animal health priorities, particularly in the governance of pandemic-scale zoonotic infectious disease threats. However, the policy challenges of integrating public health and animal health priorities in the context of trade and development issues remain relatively unexamined, and few studies to date have explored the implications of global disease governance for resource-constrained countries outside the main centres of zoonotic outbreaks. This article draws on a policy study of national level avian and pandemic influenza preparedness between 2005 and 2009 across the sectors of trade, health and agriculture in Zambia. We highlight the challenges of integrating disease control interventions amidst trade and developmental realities in resource-poor environments. One Health prioritizes disease risk mitigation, sidelining those trade and development narratives which speak to broader public health concerns. We show how locally important trade and development imperatives were marginalized in Zambia, limiting the effectiveness of pandemic preparedness. Our findings are likely to be generalizable to other resource-constrained countries, and suggest that effective disease governance requires alignment with trade and development sectors, as well as integration of veterinary and public health sectors.

PMID: 24532120 [PubMed - indexed for MEDLINE]

http://ift.tt/2fVdNGi

Successful Treatment of Rhino-Orbital-Cerebral Mucormycosis in a Child With Leukemia.

Successful Treatment of Rhino-Orbital-Cerebral Mucormycosis in a Child With Leukemia.

J Pediatr Hematol Oncol. 2016 Nov 10;

Authors: Jensen TS, Arendrup MC, von Buchvald C, Frandsen TL, Juhler M, Nygaard U

Abstract
Rhino-orbital-cerebral mucormycosis (ROCM) is a rare fulminant opportunistic fungal infection that despite relevant treatment has high mortality. We present a case of a 3-year-old girl with acute lymphoblastic leukemia and ROCM, who was treated successfully with excessive surgery, systemic antifungal treatment with amphotericin B (AmB), posaconazole, and terbinafine as well as hyperbaric oxygen. Surgery included, beside extracranial and intracranial removal of infected areas, endoscopic sinus and skull base surgery with local AmB installation and in addition placement of an Ommaya reservoir for 114 intrathecal administrations of AmB. In addition, we review the literature of ROCM in pediatric patients with hematological diseases.

PMID: 27841827 [PubMed - as supplied by publisher]

http://ift.tt/2eB359S

Recurrent skull base rhabdoid meningioma in an adolescent patient.

Recurrent skull base rhabdoid meningioma in an adolescent patient.

Neurol India. 2016 Nov-Dec;64(6):1365-1369

Authors: Ghosh R, Dutta D, Dasgupta S, Chatterjee U, Chatterjee S, Chaudhuri MK

PMID: 27841231 [PubMed - in process]

http://ift.tt/2fVdNWO

Issue Information - Contents

http://ift.tt/2fSmrDI

The Effectiveness of Low-Level Light Therapy in Attenuating Vocal Fatigue.

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The Effectiveness of Low-Level Light Therapy in Attenuating Vocal Fatigue.

J Voice. 2016 Nov 7;:

Authors: Kagan LS, Heaton JT

Abstract
OBJECTIVES: Low-level light therapy (LLLT) is effective in reducing inflammation, promoting wound healing, and preventing tissue damage, but has not yet been studied in the treatment of voice disorders. The objective of this study was to investigate the possible effectiveness of LLLT in attenuating symptoms of vocal fatigue created by a vocal loading task as measured by acoustic, aerodynamic, and self-reported vocal effort.
METHODS: In a randomized, prospective study, 16 vocally healthy adults divided into four groups underwent a 1-hour vocal loading procedure, followed by infrared wavelength LLLT (828 nm), red wavelength LLLT (628 nm), heat, or no heat-light (control) treatment targeting the laryngeal region of the ventral neck surface. Phonation threshold pressure (PTP), relative fundamental frequency (RFF), and the inability to produce soft voice (IPSV) self-perceptual rating scale were recorded (1) at baseline, (2) immediately after vocal loading, (3) after treatment, and (4) 1 hour after treatment.
RESULTS: Vocal loading significantly increased PTP and IPSV and decreased onset and offset RFFs, consistent with a shift toward vocal dysfunction. Red light significantly normalized the combination of PTP, IPSV, and RFF measures compared to other conditions.
CONCLUSIONS: RFF is sensitive to a vocal loading task in conjunction with PTP and IPSV, and red LLLT may have a normalizing effect on objective and subjective measures of vocal fatigue. The results of this study lay the groundwork and rationale for future research to optimize LLLT wavelength combinations and overall dose.

PMID: 27839705 [PubMed - as supplied by publisher]

http://ift.tt/2f0nBzk

Management of lateral skull base cancer: United Kingdom National Multidisciplinary Guidelines.

Management of lateral skull base cancer: United Kingdom National Multidisciplinary Guidelines.

J Laryngol Otol. 2016 May;130(S2):S119-S124

Authors: Homer JJ, Lesser T, Moffat D, Slevin N, Price R, Blackburn T

Abstract
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It provides recommendations on the work up and management of lateral skull base cancer based on the existing evidence base for this rare condition. Recommendations • All patients with more than one of: chronic otalgia, bloody otorrhoea, bleeding, mass, facial swelling or palsy should be biopsied. (R) • Magnetic resonance and computed tomography imaging should be performed. (R) • Patients should undergo audiological assessment. (R) • Carotid angiography is recommended in select patients. (G) • The modified Pittsburg T-staging system is recommended. (G) • The minimum operation for cancer involving the temporal bone is a lateral temporal bone resection. (R) • Facial nerve rehabilitation should be initiated at primary surgery. (G) • Anterolateral thigh free flap is the workhorse flap for lateral skull base defect reconstruction. (G) • For patients undergoing surgery for squamous cell carcinoma, at least a superficial parotidectomy and selective neck dissection should be carried out. (R).

PMID: 27841125 [PubMed - in process]

http://ift.tt/2fc9yV6

Incidence of Esophageal Carcinomas After Surgery for Achalasia: Usefulness of Long-Term and Periodic Follow-up.

Related Articles

Incidence of Esophageal Carcinomas After Surgery for Achalasia: Usefulness of Long-Term and Periodic Follow-up.

Am J Case Rep. 2016 Nov 14;17:845-849

Authors: Ota M, Narumiya K, Kudo K, Yagawa Y, Maeda S, Osugi H, Yamamoto M

Abstract
BACKGROUND Patients with esophageal achalasia are considered to be a high-risk group for esophageal carcinoma, and it has been reported that this cancer often arises at a long interval after surgery for achalasia. However, it is unclear whether esophageal carcinoma is frequent when achalasia has been treated successfully and the patient is without dysphagia. In this study, we reviewed patients with esophageal carcinoma who were detected by regular follow-up after surgical treatment of achalasia.   CASE REPORT Esophageal cancer was detected by periodic upper GI endoscopy in 6 patients. Most of them had early cancers that were treated by endoscopic resection. All 6 patients had undergone surgery for achalasia and the outcome had been rated as excellent or good. Annual follow-up endoscopy was done and the average duration of follow-up until cancer was seen after surgery was 14.3 years (range: 5 to 40 years). Five patients had early cancer. Four cases had multiple lesions.   CONCLUSIONS In conclusion, surgery for achalasia usually improves passage symptoms, but esophageal cancer still arises in some cases and the number of tumors occurring many years later is not negligible. Accordingly, long-term endoscopic follow-up is needed for detection of malignancy at an early stage.

PMID: 27840406 [PubMed - in process]

http://ift.tt/2eAZpFi

Hearing loss in children with otitis media with effusion: a systematic review.

Hearing loss in children with otitis media with effusion: a systematic review.

Int J Audiol. 2016 Nov 14;:1-12

Authors: Cai T, McPherson B

Abstract
OBJECTIVES: Otitis media with effusion (OME) is the presence of non-purulent inflammation in the middle ear. Hearing impairment is frequently associated with OME. Pure tone audiometry and speech audiometry are two of the most primarily utilised auditory assessments and provide valuable behavioural and functional estimation on hearing loss. This paper was designed to review and analyse the effects of the presence of OME on children's listening abilities.
DESIGN: A systematic and descriptive review.
STUDY SAMPLE: Twelve articles reporting frequency-specific pure tone thresholds and/or speech perception measures in children with OME were identified using PubMed, Ovid, Web of Science, ProQuest and Google Scholar search platforms.
RESULTS: The hearing loss related to OME averages 18-35 dB HL. The air conduction configuration is roughly flat with a slight elevation at 2000 Hz and a nadir at 8000 Hz. Both speech-in-quiet and speech-in-noise perception have been found to be impaired.
CONCLUSIONS: OME imposes a series of disadvantages on hearing sensitivity and speech perception in children. Further studies investigating the full range of frequency-specific pure tone thresholds, and that adopt standardised speech test materials are advocated to evaluate hearing related disabilities with greater comprehensiveness, comparability and enhanced consideration of their real life implications.

PMID: 27841699 [PubMed - as supplied by publisher]

http://ift.tt/2ftyGcY

Subcellular Patch-clamp Recordings from the Somatodendritic Domain of Nigral Dopamine Neurons.

Subcellular Patch-clamp Recordings from the Somatodendritic Domain of Nigral Dopamine Neurons.

J Vis Exp. 2016 Nov 2;(117):

Authors: Engel D

Abstract
Dendrites of dopaminergic neurons receive and convey synaptic input, support action potential back-propagation and neurotransmitter release. Understanding these fundamental functions will shed light on the information transfer in these neurons. Dendritic patch-clamp recordings provide the possibility to directly examine the electrical properties of dendrites and underlying voltage-gated ion channels. However, these fine structures are not easily accessible to patch pipettes because of their small diameter. This report describes a step-by-step procedure to collect stable and reliable recordings from the dendrites of dopaminergic neurons in acute slices. Electrophysiological measurements are combined with post hoc recovery of cell morphology. Successful experiments rely on improved preparation of slices, solutions and pipettes, adequate adjustment of the optics and stability of the pipette in contact with the recorded structure. Standard principles of somatic patch-clamp recording are applied to dendrites but with a gentler approach of the pipette. These versatile techniques can be implemented to address various questions concerning the excitable properties of dendrites.

PMID: 27842379 [PubMed - in process]

http://ift.tt/2fSpawG

Genotyping of Staphylococcus aureus by Ribosomal Spacer PCR (RS-PCR).

Genotyping of Staphylococcus aureus by Ribosomal Spacer PCR (RS-PCR).

J Vis Exp. 2016 Nov 4;(117):

Authors: Graber HU

Abstract
The ribosomal spacer PCR (RS-PCR) is a highly resolving and robust genotyping method for S. aureus that allows a high throughput at moderate costs and is, therefore, suitable to be used for routine purposes. For best resolution, data evaluation and data management, a miniaturized electrophoresis system is required. Together with such an electrophoresis system and the in-house developed software (freely available here) assignment of the pattern of bands to a genotype is standardized and straight forward. DNA extraction is simple (boiling prep), setting-up of the reactions is easy and they can be run on any standard PCR machine. PCR cycling is common except prolonged ramping and elongation times. Compared to spa typing and Multi Locus Sequence Typing (MLST), RS-PCR does not require DNA sequencing what simplifies the analysis considerably and allows a high throughput. Furthermore, the resolution for bovine strains of S. aureus is at least as good as spa typing and better than MLST or pulsed-field gel electrophoresis (PFGE). The RS-PCR data base includes presently a total of 141 genotypes and variants. The method is highly associated with the virulence gene pattern, contagiosity and pathogenicity of S. aureus strains involved in bovine mastitis. S. aureus genotype B (GTB) is contagious and causes herds problems causing large costs in the Switzerland and other European countries. All the other genotypes observed in Switzerland infect individual cows and quarters. Genotyping by RS-PCR allows the reliable prediction of the epidemiological and the pathogenic potential of S. aureus involved in bovine intramammary infection (IMI), two key factors for clinical veterinary medicine. Because of these beneficial properties together with moderate costs and a high sample throughput the goal of this publication is to give a detailed, step-by-step protocol for easily establishing and running RS-PCR for genotyping S. aureus in other laboratories.

PMID: 27842378 [PubMed - in process]

http://ift.tt/2f0v7dp

Understanding Dissolved Organic Matter Biogeochemistry Through In Situ Nutrient Manipulations in Stream Ecosystems.

Understanding Dissolved Organic Matter Biogeochemistry Through In Situ Nutrient Manipulations in Stream Ecosystems.

J Vis Exp. 2016 Oct 29;(116):

Authors: Wymore AS, Rodríguez-Cardona B, McDowell WH

Abstract
Dissolved organic matter (DOM) is a highly diverse mixture of molecules providing one of the largest sources of energy and nutrients to stream ecosystems. Yet the in situ study of DOM is difficult as the molecular complexity of the DOM pool cannot be easily reproduced for experimental purposes. Nutrient additions to streams however, have been shown to repeatedly alter the in situ and ambient DOM pool. Here we demonstrate an easily replicable field-based method for manipulating the ambient pool of DOM at the ecosystem scale. During nutrient pulse experiments changes in the concentration of both dissolved organic carbon and dissolved organic nitrogen can be examined across a wide-range of nutrient concentrations. This method allows researchers to examine the controls on the DOM pool and make inferences regarding the role and function that certain fractions of the DOM pool play within ecosystems. We advocate the use of this method as a technique to help develop a deeper understanding of DOM biogeochemistry and how it interacts with nutrients. With further development this method may help elucidate the dynamics of DOM in other ecosystems.

PMID: 27842377 [PubMed - in process]

http://ift.tt/2fSo5oX

Testing the Vascular Invasive Ability of Cancer Cells in Zebrafish (Danio Rerio).

Testing the Vascular Invasive Ability of Cancer Cells in Zebrafish (Danio Rerio).

J Vis Exp. 2016 Nov 3;(117):

Authors: Berens EB, Sharif GM, Wellstein A, Glasgow E

Abstract
Cancer cell vascular invasion and extravasation is a hallmark of metastatic progression. Traditional in vitro models of cancer cell invasion of endothelia typically lack the fluid dynamics that invading cells are otherwise exposed to in vivo. However, in vivo systems such as mouse models, though more physiologically relevant, require longer experimental timescales and present unique challenges associated with monitoring and data analysis. Here we describe a zebrafish assay that seeks to bridge this technical gap by allowing for the rapid assessment of cancer cell vascular invasion and extravasation. The approach involves injecting fluorescent cancer cells into the precardiac sinus of transparent 2-day old zebrafish embryos whose vasculature is marked by a contrasting fluorescent reporter. Following injection, the cancer cells must survive in circulation and subsequently extravasate from vessels into tissues in the caudal region of the embryo. Extravasated cancer cells are efficiently identified and scored in live embryos via fluorescence imaging at a fixed timepoint. This technique can be modified to study intravasation and/or competition amongst a heterogeneous mixture of cancer cells by changing the injection site to the yolk sac. Together, these methods can evaluate a hallmark behavior of cancer cells and help uncover mechanisms indicative of malignant progression to the metastatic phenotype.

PMID: 27842376 [PubMed - in process]

http://ift.tt/2f0tdK1

An Atmospheric Pressure Plasma Setup to Investigate the Reactive Species Formation.

An Atmospheric Pressure Plasma Setup to Investigate the Reactive Species Formation.

J Vis Exp. 2016 Nov 3;(117):

Authors: Gorbanev Y, Soriano R, O'Connell D, Chechik V

Abstract
Non-thermal atmospheric pressure ('cold') plasmas have received increased attention in recent years due to their significant biomedical potential. The reactions of cold plasma with the surrounding atmosphere yield a variety of reactive species, which can define its effectiveness. While efficient development of cold plasma therapy requires kinetic models, model benchmarking needs empirical data. Experimental studies of the source of reactive species detected in aqueous solutions exposed to plasma are still scarce. Biomedical plasma is often operated with He or Ar feed gas, and a specific interest lies in investigation of the reactive species generated by plasma with various gas admixtures (O2, N2, air, H2O vapor, etc.) Such investigations are very complex due to difficulties in controlling the ambient atmosphere in contact with the plasma effluent. In this work, we addressed common issues of 'high' voltage kHz frequency driven plasma jet experimental studies. A reactor was developed allowing the exclusion of ambient atmosphere from the plasma-liquid system. The system thus comprised the feed gas with admixtures and the components of the liquid sample. This controlled atmosphere allowed the investigation of the source of the reactive oxygen species induced in aqueous solutions by He-water vapor plasma. The use of isotopically labelled water allowed distinguishing between the species originating in the gas phase and those formed in the liquid. The plasma equipment was contained inside a Faraday cage to eliminate possible influence of any external field. The setup is versatile and can aid in further understanding the cold plasma-liquid interactions chemistry.

PMID: 27842375 [PubMed - in process]

http://ift.tt/2fSlLhH

Cover Image

The cover image, by Nader Sadeghi et al., is based on the Original Article Neoadjuvant chemotherapy and transoral surgery as a definitive treatment for oropharyngeal cancer: A feasible novel approach, DOI: 10.1002/hed.24526.

http://ift.tt/2fSqgIY

Sustained Administration of β-cell Mitogens to Intact Mouse Islets Ex Vivo Using Biodegradable Poly(lactic-co-glycolic acid) Microspheres.

Sustained Administration of β-cell Mitogens to Intact Mouse Islets Ex Vivo Using Biodegradable Poly(lactic-co-glycolic acid) Microspheres.

J Vis Exp. 2016 Nov 5;(117):

Authors: Pasek RC, Kavanaugh TE, Duvall CL, Gannon MA

Abstract
The development of biomaterials has significantly increased the potential for targeted drug delivery to a variety of cell and tissue types, including the pancreatic β-cells. In addition, biomaterial particles, hydrogels, and scaffolds also provide a unique opportunity to administer sustained, controllable drug delivery to β-cells in culture and in transplanted tissue models. These technologies allow the study of candidate β-cell proliferation factors using intact islets and a translationally relevant system. Moreover, determining the effectiveness and feasibility of candidate factors for stimulating β-cell proliferation in a culture system is critical before moving forward to in vivo models. Herein, we describe a method to co-culture intact mouse islets with biodegradable compound of interest (COI)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres for the purpose of assessing the effects of sustained in situ release of mitogenic factors on β-cell proliferation. This technique describes in detail how to generate PLGA microspheres containing a desired cargo using commercially available reagents. While the described technique uses recombinant human Connective tissue growth factor (rhCTGF) as an example, a wide variety of COI could readily be used. Additionally, this method utilizes 96-well plates to minimize the amount of reagents necessary to assess β-cell proliferation. This protocol can be readily adapted to use alternative biomaterials and other endocrine cell characteristics such as cell survival and differentiation status.

PMID: 27842374 [PubMed - in process]

http://ift.tt/2f0tpca

Removal of Drosophila Muscle Tissue from Larval Fillets for Immunofluorescence Analysis of Sensory Neurons and Epidermal Cells.

Removal of Drosophila Muscle Tissue from Larval Fillets for Immunofluorescence Analysis of Sensory Neurons and Epidermal Cells.

J Vis Exp. 2016 Nov 2;(117):

Authors: Tenenbaum CM, Gavis ER

Abstract
Drosophila larval dendritic arborization (da) neurons are a popular model for investigating mechanisms of neuronal morphogenesis. Da neurons develop in communication with the epidermal cells they innervate and thus their analysis benefits from in situ visualization of both neuronally and epidermally expressed proteins by immunofluorescence. Traditional methods of preparing larval fillets for immunofluorescence experiments leave intact the muscle tissue that covers most of the body wall, presenting several challenges to imaging neuronal and epidermal proteins. Here we describe a method for removing muscle tissue from Drosophila larval fillets. This protocol enables imaging of proteins that are otherwise obscured by muscle tissue, improves signal to noise ratio, and facilitates the use of super-resolution microscopy to study da neuron development.

PMID: 27842373 [PubMed - in process]

http://ift.tt/2eVXrdX

Assessment of Labile Organic Carbon in Soil Using Sequential Fumigation Incubation Procedures.

Assessment of Labile Organic Carbon in Soil Using Sequential Fumigation Incubation Procedures.

J Vis Exp. 2016 Oct 29;(116):

Authors: Blazier MA, Liechty HO

Abstract
Management practices and environmental changes can alter soil nutrient and carbon cycling. Soil labile organic carbon, a readily decomposable C pool, is highly sensitive to disturbance. It is also the primary substrate for soil microorganisms, which is fundamental to nutrient cycling. Due to these attributes, labile organic carbon (LOC) has been identified as an indicator parameter for soil health. Quantifying the turnover rate of LOC also aids in understanding changes in soil nutrient cycling processes. A sequential fumigation incubation method has been developed to estimate soil LOC and potential C turnover rate. The method requires fumigating soil samples and quantifying CO2-C respired during a 10 day incubation period over a series of fumigation-incubation cycles. Labile organic C and potential C turnover rate are then extrapolated from accumulated CO2 with a negative exponential model. Procedures for conducting this method are described.

PMID: 27842372 [PubMed - in process]

http://ift.tt/2fSpAn1

Techniques for Imaging Prometaphase and Metaphase of Meiosis I in Fixed Drosophila Oocytes.

Techniques for Imaging Prometaphase and Metaphase of Meiosis I in Fixed Drosophila Oocytes.

J Vis Exp. 2016 Oct 31;(116):

Authors: Radford SJ, McKim KS

Abstract
Chromosome segregation in human oocytes is error prone, resulting in aneuploidy, which is the leading genetic cause of miscarriage and birth defects. The study of chromosome behavior in oocytes from model organisms holds much promise to uncover the molecular basis of the susceptibility of human oocytes to aneuploidy. Drosophila melanogaster is amenable to genetic manipulation, with over 100 years of research, community, and technique development. Visualizing chromosome behavior and spindle assembly in Drosophila oocytes has particular challenges, however, due primarily to the presence of membranes surrounding the oocyte that are impenetrable to antibodies. We describe here protocols for the collection, preparation, and imaging of meiosis I spindle assembly and chromosome behavior in Drosophila oocytes, which allow the molecular dissection of chromosome segregation in this important model organism.

PMID: 27842371 [PubMed - in process]

http://ift.tt/2f0v5SP

Using Touch-evoked Response and Locomotion Assays to Assess Muscle Performance and Function in Zebrafish.

Using Touch-evoked Response and Locomotion Assays to Assess Muscle Performance and Function in Zebrafish.

J Vis Exp. 2016 Oct 31;(116):

Authors: Sztal TE, Ruparelia AA, Williams C, Bryson-Richardson RJ

Abstract
Zebrafish muscle development is highly conserved with mammalian systems making them an excellent model to study muscle function and disease. Many myopathies affecting skeletal muscle function can be quickly and easily assessed in zebrafish over the first few days of embryogenesis. By 24 hr post-fertilization (hpf), wildtype zebrafish spontaneously contract their tail muscles and by 48 hpf, zebrafish exhibit controlled swimming behaviors. Reduction in the frequency of, or other alterations in, these movements may indicate a skeletal muscle dysfunction. To analyze swimming behavior and assess muscle performance in early zebrafish development, we utilize both touch-evoked escape response and locomotion assays. Touch-evoked escape response assays can be used to assess muscle performance during short burst movements resulting from contraction of fast-twitch muscle fibers. In response to an external stimulus, which in this case is a tap on the head, wildtype zebrafish at 2 days post-fertilization (dpf) typically exhibit a powerful burst swim, accompanied by sharp turns. Our method quantifies skeletal muscle function by measuring the maximum acceleration during a burst swimming motion, the acceleration being directly proportional to the force produced by muscle contraction. In contrast, locomotion assays during early zebrafish larval development are used to assess muscle performance during sustained periods of muscle activity. Using a tracking system to monitor swimming behavior, we obtain an automated calculation of the frequency of activity and distance in 6-day old zebrafish, reflective of their skeletal muscle function. Measurements of swimming performance are valuable for phenotypic assessment of disease models and high-throughput screening of mutations or chemical treatments affecting skeletal muscle function.

PMID: 27842370 [PubMed - in process]

http://ift.tt/2fSmnUj

Fluorescence-activated Cell Sorting for Purification of Plasmacytoid Dendritic Cells from the Mouse Bone Marrow.

Fluorescence-activated Cell Sorting for Purification of Plasmacytoid Dendritic Cells from the Mouse Bone Marrow.

J Vis Exp. 2016 Nov 4;(117):

Authors: Liao X, Makris M, Luo XM

Abstract
Fluorescence-activated cell sorting (FACS) is a technique to purify specific cell populations based on phenotypes detected by flow cytometry. This method enables researchers to better understand the characteristics of a single cell population without the influence of other cells. Compared to other methods of cell enrichment, such as magnetic-activated cell sorting (MCS), FACS is more flexible and accurate for cell separation due to the ability of phenotype detection by flow cytometry. In addition, FACS is usually capable of separating multiple cell populations simultaneously, which improves the efficiency and diversity of experiments. Although FACS has some limitations, it has been broadly used to purify cells for functional studies in both in vitro and in vivo settings. Here we report a protocol using fluorescence-activated cell sorting to isolate a very rare population of immune cells, plasmacytoid dendritic cells (pDC), with high purity from the bone marrow of lupus-prone mice for in vitro functional studies of pDC.

PMID: 27842369 [PubMed - in process]

http://ift.tt/2f0pJY4

Analysis of Protein Import into Chloroplasts Isolated from Stressed Plants.

Analysis of Protein Import into Chloroplasts Isolated from Stressed Plants.

J Vis Exp. 2016 Nov 1;(117):

Authors: Ling Q, Jarvis P

Abstract
Chloroplasts are organelles with many vital roles in plants, which include not only photosynthesis but numerous other metabolic and signaling functions. Furthermore, chloroplasts are critical for plant responses to various abiotic stresses, such as salinity and osmotic stresses. A chloroplast may contain up to ~3,000 different proteins, some of which are encoded by its own genome. However, the majority of chloroplast proteins are encoded in the nucleus and synthesized in the cytosol, and these proteins need to be imported into the chloroplast through translocons at the chloroplast envelope membranes. Recent studies have shown that the chloroplast protein import can be actively regulated by stress. To biochemically investigate such regulation of protein import under stress conditions, we developed the method described here as a quick and straightforward procedure that can easily be achieved in any laboratory. In this method, plants are grown under normal conditions and then exposed to stress conditions in liquid culture. Plant material is collected, and chloroplasts are then released by homogenization. The crude homogenate is separated by density gradient centrifugation, enabling isolation of the intact chloroplasts. Chloroplast yield is assessed by counting, and chloroplast intactness is checked under a microscope. For the protein import assays, purified chloroplasts are incubated with (35)S radiolabeled in vitro translated precursor proteins, and time-course experiments are conducted to enable comparisons of import rates between genotypes under stress conditions. We present data generated using this method which show that the rate of protein import into chloroplasts from a regulatory mutant is specifically altered under osmotic stress conditions.

PMID: 27842368 [PubMed - in process]

http://ift.tt/2fSrZhv

A Buoyancy-based Method of Determining Fat Levels in Drosophila.

A Buoyancy-based Method of Determining Fat Levels in Drosophila.

J Vis Exp. 2016 Nov 1;(117):

Authors: Hazegh KE, Reis T

Abstract
Drosophila melanogaster is a key experimental system in the study of fat regulation. Numerous techniques currently exist to measure levels of stored fat in Drosophila, but most are expensive and/or laborious and have clear limitations. Here, we present a method to quickly and cheaply determine organismal fat levels in L3 Drosophila larvae. The technique relies on the differences in density between fat and lean tissues and allows for rapid detection of fat and lean phenotypes. We have verified the accuracy of this method by comparison to body fat percentage as determined by neutral lipid extraction and gas chromatography coupled with mass spectrometry (GCMS). We furthermore outline detailed protocols for the collection and synchronization of larvae as well as relevant experimental recipes. The technique presented below overcomes the major shortcomings in the most widely used lipid quantitation methods and provides a powerful way to quickly and sensitively screen L3 larvae for fat regulation phenotypes while maintaining the integrity of the larvae. This assay has wide applications for the study of metabolism and fat regulation using Drosophila.

PMID: 27842367 [PubMed - in process]

http://ift.tt/2f0pBHH

Ultrasound Assessment of Flow-Mediated Dilation of the Brachial and Superficial Femoral Arteries in Rats.

Ultrasound Assessment of Flow-Mediated Dilation of the Brachial and Superficial Femoral Arteries in Rats.

J Vis Exp. 2016 Nov 3;(117):

Authors: Machin DR, Leary ME, He Y, Shiu YT, Tanaka H, Donato AJ

Abstract
Arterial vasodilation to increases in wall shear rate is indicative of vascular endothelial function. In humans, the non-invasive measurement of endothelial function can be achieved by employing the flow-mediated dilation technique, typically performed in the brachial or superficial femoral artery. Briefly, a blood pressure cuff placed distal to an ultrasound probe is inflated to a suprasystolic pressure, which results in limb ischemia. After 5 min of occlusion the cuff is deflated, resulting in reactive hyperemia and increases in wall shear rate that signal vasodilatory molecules to be released from the endothelium eliciting vasodilation. Despite the thousands of studies performing flow-mediated dilation in humans, surprisingly, no studies have performed this technique non-invasively in living rats. Considering the recent shift in focus to translational research, the establishment of guidelines for non-invasive measurement of flow-mediated dilation in rats and other rodents would be extremely valuable. In the following article, a protocol is presented for the non-invasive measurement of flow-mediated dilation in brachial and superficial femoral arteries of rats, as those sites are most commonly measured in humans.

PMID: 27842366 [PubMed - in process]

http://ift.tt/2fStI6k

An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity.

An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity.

J Vis Exp. 2016 Nov 2;(117):

Authors: Bolt HL, Denny PW, Cobb SL

Abstract
This protocol describes the manual solid-phase synthesis of linear peptoids that contain two differently functionalized cationic monomers. In this procedure amino functionalized 'lysine' and guanido functionalized 'arginine' peptoid monomers can be included within the same peptoid sequence. This procedure uses on-resin (N-(1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl) or Dde protection, orthogonal conditions to the Boc protection of lysine monomers. Subsequent deprotection allows an efficient on-resin guanidinylation reaction to form the arginine residues. The procedure is compatible with the commonly used submonomer method of peptoid synthesis, allowing simple peptoids to be made using common laboratory equipment and commercially available reagents. The representative synthesis, purification and characterization of two mixed peptoids is described. The evaluation of these compounds as potential anti-infectives in screening assays against Leishmania mexicana is also described. The protozoan parasite L. mexicana is a causative agent of cutaneous leishmaniasis, a neglected tropical disease that affects up to 12 million people worldwide.

PMID: 27842365 [PubMed - in process]

http://ift.tt/2f0pBYp

Methyl-binding DNA capture Sequencing for Patient Tissues.

Methyl-binding DNA capture Sequencing for Patient Tissues.

J Vis Exp. 2016 Oct 31;(116):

Authors: Jadhav RR, Wang YV, Hsu YT, Liu J, Garcia D, Lai Z, Huang TH, Jin VX

Abstract
Methylation is one of the essential epigenetic modifications to the DNA, which is responsible for the precise regulation of genes required for stable development and differentiation of different tissue types. Dysregulation of this process is often the hallmark of various diseases like cancer. Here, we outline one of the recent sequencing techniques, Methyl-Binding DNA Capture sequencing (MBDCap-seq), used to quantify methylation in various normal and disease tissues for large patient cohorts. We describe a detailed protocol of this affinity enrichment approach along with a bioinformatics pipeline to achieve optimal quantification. This technique has been used to sequence hundreds of patients across various cancer types as a part of the 1,000 methylome project (Cancer Methylome System).

PMID: 27842364 [PubMed - in process]

http://ift.tt/2fSl5J4