Παρασκευή 9 Σεπτεμβρίου 2016

Effects of wearing and removing dentures on oropharyngeal motility during swallowing

Abstract

Background

Wearing dentures and dysphagia are common in older individuals, however, it is still unknown how dentures affects oral and pharyngeal swallowing.

Objectives

The purpose of this study was to reveal the effects of wearing and removing dentures on oropharygeal movements during pharyngeal swallowing in the feeding sequence of solid food.

Methods

Participants were 25 edentulous volunteers (9 men, 16 women; mean age 76.2 years) who wore complete dentures. The test food was minced agar jelly containing barium sulfate. Subjects were instructed to feed and swallow the test food with or without dentures during observation using videofluorography. We quantitatively evaluated the range, distance, and duration of oropharyngeal movements during pharyngeal swallowing.

Results

When dentures were absent, the range of mandible and hyoid movements were significantly expanded in the anterosuperior direction, and the range of laryngeal movement was significantly expanded in the anterior direction. Additionally, the posterior pharyngeal wall contraction and upper esophageal sphincter opening significantly increased. In addition, the distances of the mandible, hyoid, and laryngeal movements, and the mandibular duration were significantly extended when dentures were absent. No significant differences were observed in the duration of movements of other organs between wearing and removing dentures.

Conclusions

The hyoid bone, larynx, posterior pharyngeal wall, and upper esophageal sphincter do not change their duration of movements when dentures were removed, but rather, expand their range of movement. This might be spatial change of oropharyngeal movement to avoid temporal changes in pharyngeal swallowing when dentures were absent in edentulous older individuals.

This article is protected by copyright. All rights reserved.



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Doing a Community Healthcare Assessment

Dr. Wilcox details first steps to successfully implement a community healthcare program (community paramedicine).

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Doing a Community Healthcare Assessment

Dr. Wilcox details first steps to successfully implement a community healthcare program (community paramedicine).

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Doing a Community Healthcare Assessment

Dr. Wilcox details first steps to successfully implement a community healthcare program (community paramedicine).

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Publishers' note



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What increased passenger vehicle miles means for EMS and fire departments

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In life, precious little happens in isolation. Any action nearly always brings both intended and unintended reactions. So when I heard a news story about low gasoline prices come over the radio while driving, I figured there was a catch.

And there was.

The sustained lower fuel prices have pushed fuel consumption above record levels — in other words people are driving more presumably because it's cheaper. The other thing they are doing more often is crashing.

And those crashes they are having are worse if you measure severity by the number of fatalities and injuries. The National Highway Transportation Safety Administration released a report last week on the number of people killed and injured in vehicle crashes during 2015.

The numbers for both are up for the first time since start of the Great Recession. Motor vehicle crash fatalities are up 7.2 percent and injuries are up 4.5 percent compared with 2014.

Drowsy driving was the only category of human-behavior causes that decreased for fatalities and injuries — not wearing restraints and distracted driving were among the categories that increased, 4.9 percent and 8.8 percent, respectively.

The National Public Radio news report I was listening to cited Federal Highway Administration numbers that showed Americans are driving more — 3 percent more this June compared with last June.

Of course, for fire departments, this creeping increase in the number of vehicle crashes means more MVC responses. If this trend holds, some departments will have to adjust their planning and resource allocation. And of course, this is best done in anticipation of the changes rather than in reaction to them.

The NPR story floated the notion that increased driving trend would continue if fuel prices rose. The logic is that federal mandates on improved fuel mileage will reduce the amount owners spend on fuel.

While I have no data to back this, my gut tells me that consumers will adjust driving habits more based the price they see at the pump than their monthly gasoline expenses.

That aside, fire departments can begin thinking of what changes they will make if vehicle crashes do continue to increase. Some of that may involve charting MVC run reports by month, quarter and year and across different sections of the jurisdiction to identify the need for additional or reallocated rescue resources.

It can also include looking at vehicle and rescue equipment replacement schedules to see if shortening those is warranted. And it may mean additional training for departments that don't perform many extrications.

Most importantly, it will require that departments revisit their on-scene safety practices. Roadside incidents have been and remain a high risk, high frequency threat.

Motorists driving more miles not only means more initial crashes, it raises the potential for those deadly secondary crashes that we all dread. After all, few things in life happen in isolation.

About the author

Rick Markley is editor-in-chief of FireRescue1 and Fire Chief, a volunteer firefighter and fire investigator. He serves on the board of directors of and is actively involved with the International Fire Relief Mission, a humanitarian aid organization that delivers unused fire and EMS equipment to firefighters in developing countries. He holds a bachelor's degree in communications and a master's of fine arts. He has logged more than 10 years as an editor-in-chief and written numerous articles on firefighting. He can be reached at Rick.Markley@FireRescue1.com.



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Doing a Community Healthcare Assessment

Dr. Wilcox details first steps to successfully implement a community healthcare program (community paramedicine).

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Inpatient Paramedic Transporter - Florida Hospital

Job Summary: As a Paramedic, you will make providing service your priority while caring for the whole person in a faith-based atmosphere The Advanced Technician II performs patient care under the direction of and as assigned by the Charge nurse, registered nurse and/or physician or their designee. Performs general clinical, non-clinical and clerical services necessary to expedite the efficient functioning ...

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Mechanism of allele specific assembly and disruption of master regulator transcription factor complexes of NF-KBp50, NF-KBp65 and HIF1a on a non-coding FAS SNP

Publication date: Available online 9 September 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Chidiebere U. Awah, Stefanie Tamm, Silke Hedtfeld, Doris Steinemann, Burkhard Tümmler, Georgios Tsiavaliaris, Frauke Stanke
A challenging question in genetics is to understand the molecular function of non-coding variants of the genome. By using differential EMSA, ChIP and functional genome analysis, we have found that changes in transcription factors (TF) apparent binding affinity and dissociation rates are responsible for allele specific assembly or disruption of master TFs: we observed that NF-KBp50, NF-KBp65 and HIF1a bind with an affinity of up to 10 fold better to the C-allele than to the T-allele of rs7901656 both in vivo and in vitro. Furthermore, we showed that NF-KBp50, p65 and HIF1a form higher order heteromultimeric complexes overlapping rs7901656, implying synergism of action among TFs governing cellular response to infection and hypoxia. With rs7901656 on the FAS gene as a paradigm, we show how allele specific transcription factor complex assembly and disruption by a causal variant contributes to disease and phenotypic diversity. This finding provides the highly needed mechanistic insight into how the molecular etiology of regulatory SNPs can be understood in functional terms.

Graphical abstract

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Differences in post-exercise T2 relaxation time changes between eccentric and concentric contractions of the elbow flexors

Abstract

Purpose

This study compared maximal eccentric (ECC) and concentric (CON) contractions of the elbow flexors for changes in transverse relaxation time (T2) and indirect markers of muscle damage.

Methods

Twelve young men performed five sets of six maximal isokinetic (30°/s) ECC with one arm followed by CON with the other arm. Magnetic resonance images to assess T2 and cross-sectional area (CSA) of biceps brachii, brachialis, and brachioradialis, and measurements of maximal voluntary isometric contraction (MVC) torque, range of motion (ROM), and muscle soreness were taken before, immediately after, and 1, 3, and 5 days after each exercise.

Results

MVC torque and ROM decreased greater after ECC than CON (p < 0.05), and muscle soreness developed only after ECC. Biceps brachii and brachialis CSA increased immediately after CON, but delayed increases in brachialis CSA were found only after ECC (p < 0.05). T2 of the muscles increased greater after CON (27–34 %) than ECC (16–18 %) immediately post-exercise (p < 0.05), but returned to baseline by 1 day after CON. The biceps brachii and brachialis T2 increased by 9–29 % at 1–5 days after ECC (p < 0.05). The post-ECC T2 changes showed no significant correlations with the changes in MVC torque, muscle soreness, and CSA, but the T2 increase immediately post-ECC was correlated with the peak T2 in 1–5-day post-ECC (r = 0.63, p < 0.05).

Conclusion

These results suggest that muscle activity during exercise was lower in ECC than CON, and the T2 changes after ECC do not necessarily relate to the changes in other indirect markers of muscle damage.



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Current treatment approaches for ankle ligament injuries: what has changed?

2016-09-09T03-54-32Z
Source: Medicine Science | International Medical Journal
Bulent Karslioglu, Taner Dandinoglu, Yusuf Erdem, Ozgur Dandin.
Because of inadequate and unsuccesful management of ALI, undesired chronic disabilities may unluckily be observed. Treatment of these patients should be planned comprehensive and detailed depending on patients diagnosis, injurys severity and stage. Program should not only be focused on to solve edema. An integrated treatment covering injurys acute and subacute period and a comprehensive algorithm including an early rehabilitation program would provide better recovery times.


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Longer tourniquet application time decreases the quadriceps muscle strength: a prospective study on 25 consecutive patients underwent total knee arthroplasty

2016-09-09T03-54-32Z
Source: Medicine Science | International Medical Journal
Gokay Gormeli, Emin Ertugrul Sener, Sezai Aykin Simsek, Mehmet Ali Deveci, Jale Meray.
The use of tourniquets in total knee arthroplasty (TKA) for patients with knee osteoarthritis is controversial. Although surgical techniques are more easily applied in a shorter time; there are some disadvantages associated with tourniquet use in orthopedic surgery. The aim of this study was to evaluate the effect of the tourniquet time on quadriceps strength by isokinetic muscle strength measurements in patients undergoing TKA. Prospective controlled study. Twenty-five knees of 25 patients with primary degenerative joint disease who underwent TKA were evaluated preoperatively and postoperatively at weeks 6 and 12 and month 6 by isokinetic knee extensor muscle strength testing at and American Knee Society Score (AKSS). The tourniquet time of all patients was recorded, and the preoperative results of all patients were compared with those postoperatively. The mean 60º/s angular velocity quadriceps peak torque was significantly lower postoperatively in patients with a longer tourniquet time. Isokinetic tests showed a significant negative correlation between the tourniquet time and mean muscle strength (week 6: r = 0.718, p

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Nerve Conduction Studies In Lower Limb Weakness

2016-09-09T03-28-49Z
Source: National Journal of Integrated Research in Medicine
Dr Sangeeta Jain*, Dr Vijay Vaidya**, Dr Mukesh Dinkar***, Dr Balaji Ghugare Asst****, Dr Manjiri Joshi*****.
Introduction: Nerve conduction studies (NCS) are an essential part of the work-up of peripheral neuropathies. NCS with EMG allows diagnostic classification, understanding and separation of different neuropathies. Symmetrical lower limb weakness of neurological origin often demands EDX study. Neuropathies may be mixed or motor or sensory. Further it may be either axonal or demyelinating. Aims and objectives: To assess nerve conduction studies in symmetrical lower limb weakness patients with peripheral neuropathies. To estimate prevalence of neuropathies in this cohort. Material methods: Forty cases and equal no of controls underwent NCV study. Tibial peroneal motor and sural sensory nerve conductions were done. Data was stored in excel sheet for analysis. Different NCV variables were compared between the groups. Unpaired ttest was used for comparison of variables. Level of significance was kept at p value


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Primary tumor resection following favorable response to systemic chemotherapy in stage IV pancreatic adenocarcinoma with synchronous metastases: A bi-institutional analysis

Journal of Gastrointestinal Surgery

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Effectiveness and safety of daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: Systematic review and meta-analysis

Journal of Gastroenterology and Hepatology

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Prognostic Nutritional Index predicts short-term postoperative outcomes after bowel resection for Crohn's disease

Nutrition in Clinical Practice

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Improving survival and local control in rectal cancer in Catalonia (Spain) in the context of centralisation: A full cycle audit assessment

European Journal of Surgical Oncology

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Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: A systematic review and meta-analysis

BMC Cancer

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Laparoscopic repair of sliding inguinal hernia in female children

Pediatric Surgery International

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Effect of diet based on the principles of Iranian Traditional Medicine on cirrhosis (A clinical trial)

Complementary Therapies in Medicine

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Diagnosis and surgical management of insulinomas in 33 consecutive patients at a single institution

Langenbeck's Archives of Surgery

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Pepsin in saliva as a biomarker for oropharyngeal reflux compared with 24-hour esophageal impedance/pH monitoring in pediatric patients

Neurogastroenterology & Motility

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The effect of morbid obesity on morphine glucuronidation

Pharmacological Research

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The race-specific incidence of esophageal squamous cell carcinoma in individuals with exposure to tobacco and alcohol

The American Journal of Gastroenterology

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In vivo assessment by parents and a physician using the Amsterdam Infant Stool Scale provided better inter-rater agreement than photographic evaluation

Acta Pediatrica

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Fruit and vegetable consumption and risk of cholecystectomy: A prospective cohort study of women and men

European Journal of Nutrition

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Falciform ligament wrap for prevention of gastroduodenal artery bleed after pancreatoduodenectomy

Journal of Surgical Research

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Efficacy of ethanol locks to reduce the incidence of catheter-related bloodstream infections for home parenteral nutrition pediatric patients: Comparison of therapeutic treatment with prophylactic treatment

Pediatric Surgery International

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Emergency management with resection versus proximal stoma or stent treatment and planned resection in malignant left-sided colon obstruction

World Journal of Surgical Oncology

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Inflammatory bowel diseases (Crohn´s disease and ulcerative colitis): Cost of treatment in Serbia and the implications

Applied Health Economics and Health Policy

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Colorectal cancer in the very young: A comparative study of tumor markers, pathology and survival in early onset and adult onset patients

Journal of Pediatric Surgery

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Effect of fecal microbiota transplantation on recurrence in multiply recurrent Clostridium difficile infection: A randomized trial

Annals of Internal Medicine

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24-h multichannel intraluminal impedance pH-metry 1 year after laparocopic sleeve gastrectomy: An objective assessment of gastroesophageal reflux disease

Obesity Surgery

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The influence of statins on osseointegration: a systematic review of animal-model studies

Abstract

The increase in the use of immediately loaded dental implants and implant anchorage in low-density bone tissue has led to a need for accelerating and improving the osseointegration process. In some groups, such as osteoporosis patients, this need may be even greater. Previous investigations have demonstrated that osteoporosis can impair the process of osseointegration in an experimental model1,2. In this context, several studies have reported strategies to enhance osseointegration, such as the use of growth factor and/or stem cells, hormone replacement, the development of nanosurfaces and nanotechnology, the use of new titanium alloys, surface chemistry and the use of drugs.

This article is protected by copyright. All rights reserved.



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Influence of preoperative oral rehydration on arterial plasma rocuronium concentrations and neuromuscular blocking effects: A randomised controlled trial.

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BACKGROUND: The influence of preoperative rehydration on the action of rocuronium has not yet been investigated. OBJECTIVE: The objective is to evaluate the hypothesis that preoperative rehydration lowers arterial rocuronium plasma concentrations and changes its associated neuromuscular blocking effects during induction of anaesthesia. DESIGN: Randomised, single-blinded study. SETTING: A secondary hospital from October 2013 to July 2014. PATIENTS: In total, 46 men undergoing elective surgery were eligible to participate and were randomly allocated into two groups. Exclusion criteria were severe hepatic, renal or cardiovascular disorder; neuromuscular disease; history of allergy to rocuronium; BMI more than 30 kg m-2; receiving medication known to influence neuromuscular function. INTERVENTION: Participants received 1500 ml of oral rehydration solution (rehydration group) or none (control group) until 2 hours before anaesthesia. Arterial blood samples were obtained 60, 90 and 120 s and 30 min after rocuronium (0.6 mg kg-1) administration during total intravenous anaesthesia. Responses to 0.1-Hz twitch stimuli were measured at the adductor pollicis muscle using acceleromyography. MAIN OUTCOME MEASURES: Arterial plasma rocuronium concentrations. RESULTS: Arterial plasma rocuronium concentrations at 60, 90 and 120 s in the rehydration and control groups were 9.9 and 13.7, 6.8 and 9.5 and 6.2 and 8.1 [mu]g ml-1, respectively (P = 0.02, 0.003 and 0.02, respectively); the onset times in the rehydration and control groups were 92.0 and 69.5 s (P = 0.01), and the times to twitch re-appearance were 25.3 and 30.4 min (P = 0.004), respectively. CONCLUSION: Preoperative rehydration significantly reduces arterial plasma rocuronium concentrations in the first 2 minutes after administration, prolonging the onset time and shortening the duration of effect. A higher dose or earlier administration should be considered for patients who receive preoperative rehydration. TRIAL REGISTRATION: Umin identifier: UMIN000011981. (C) 2016 European Society of Anaesthesiology

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Determination of loss of consciousness: a comparison of clinical assessment, bispectral index and electroencephalogram: An observational study.

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BACKGROUND: Computer-processed algorithms of encephalographic signals are widely used to assess the depth of anaesthesia. However, data indicate that the bispectral index (BIS), a processed electroencephalography monitoring system, may not be reliable for assessing the depth of anaesthesia. OBJECTIVE: The aim of this study was to evaluate the ability of the BIS monitoring system to assess changes in the level of unconsciousness, specifically during the transition from consciousness to unconsciousness, in patients undergoing total intravenous anaesthesia with propofol. We compared BIS with the electroencephalogram (EEG), and clinical loss of consciousness (LOC) defined as loss of verbal commands and eyelash reflex. DESIGN: This was an observational cohort study. SETTING: University Hospital Linkoping, University Hospital Orebro, Finspang Hospital and Kalmar Hospital, Sweden from October 2011 to April 2013. PATIENTS: A total of 35 ASA I patients aged 18 to 49 years were recruited. INTERVENTIONS: The patients underwent total intravenous anaesthesia with propofol and remifentanil for elective day-case surgery. Changes in clinical levels of consciousness were assessed by BIS and compared with assessment of stage 3 neurophysiological activity using the EEG. The plasma concentrations of propofol were measured at clinical LOC and 20 and 30 min after LOC. MAIN OUTCOME MEASURES: The primary outcome was measurement of BIS, EEG and clinical LOC. RESULTS: The median BIS value at clinical LOC was 38 (IQR 30 to 43), and the BIS values varied greatly between patients. There was no correlation between BIS values and EEG stages at clinical LOC (r = -0.1, P = 0.064). Propofol concentration reached a steady state within 20 min. CONCLUSION: There was no statistically significant correlation between BIS and EEG at clinical LOC. BIS monitoring may not be a reliable method for determining LOC. CLINICAL TRIALS REGISTRY: This trial was not registered because registration was not mandatory at the time of the trial. (C) 2016 European Society of Anaesthesiology

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Three-Dimensional Transthoracic Echocardiography for Evaluation of Mitral Stenosis Identification of Severe Mitral Stenosis Using Real-Time Three-Dimensional Transesophageal Echocardiography During an Left Ventricular Assist Device Insertion.

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No abstract available

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Long-Acting Patient-Controlled Opioids Are Not Associated With More Postoperative Hypoxemia Than Short-Acting Patient-Controlled Opioids After Noncardiac Surgery: A Cohort Analysis.

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BACKGROUND: Opioids can contribute to postoperative desaturation. Short-acting opioids, titrated to need, may cause less desaturation than longer-acting opioids. We thus tested the primary hypothesis that long-acting patient-controlled intravenous opioids are associated with more hypoxemia (defined as an integrated area under a postoperative oxyhemoglobin saturation of 95%) than short-acting opioids. METHODS: This analysis was a substudy of VISION, a prospective cohort study focused on perioperative cardiovascular events (NCT00512109). After excluding for predefined criteria, 191 patients were included in our final analysis, with 75 (39%) patients being given fentanyl (short-acting opioid group) and 116 (61%) patients being given morphine and/or hydromorphone (long-acting opioid group). The difference in the median areas under a postoperative oxyhemoglobin saturation of 95% between short-acting and long-acting opioids was compared using multivariable median quantile regression. RESULTS: The short-acting opioid median area under a postoperative oxyhemoglobin saturation of 95% per hour was 1.08 (q1, q3: 0.62, 2.26) %-h, whereas the long-acting opioid median was 1.28 (0.50, 2.23) %-h. No significant association was detected between long-acting and short-acting opioids and median area under a postoperative oxyhemoglobin saturation of 95% per hour (P = .66) with estimated change in the medians of -0.14 (95% CI, -0.75, 0.47) %-h for the patients given long-acting versus short-acting IV patient-controlled analgesia opioids. CONCLUSIONS: Long-acting patient-controlled opioids were not associated with the increased hypoxemia during the first 2 postoperative days. (C) 2016 International Anesthesia Research Society

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Structural Integrity of a Simple Method to Repair Disrupted Tracheal Tube Pilot Balloon Assemblies.

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BACKGROUND: An intact pilot balloon assembly is crucial to the proper function of a cuffed tracheal tube. Disruption of the pilot balloon, transection of the inflation line, or valve incompetence results in cuff deflation, which may lead to inadequate ventilation and aspiration of secretions. Such failures typically result in tracheal tube replacement, but this may be a safety risk if a difficult reintubation is anticipated. We recently encountered such a patient who remained intubated postoperatively and in whom the inflation line was transected, causing a large leak. We describe a method to reconstitute the inflation line and report on the structural integrity of the repair. We hypothesized that the repaired assembly would maintain cuff pressure not statistically different from an intact device, but that the inflation line would be weaker. METHODS: The distal (tapered) portion of a 22-gauge intravenous (IV) catheter was partially inserted into the severed end of the inflation line. A new pilot balloon was cut from an intact tracheal tube with the tubing attached, the end of which had been dilated using a 22-gauge IV catheter. The new tubing was then guided over the protruding portion of the catheter, creating an internal stent. We measured the drop in cuff pressure after 8 hours in an artificial trachea for repaired and intact tracheal tubes. We tested the integrity of the repaired segments, underwater, to high-pressure inflation. We measured the static tensile strength of the inflation line from intact and repaired tracheal tubes. Data are presented as the mean +/- standard error. Differences were assessed using the unpaired, 2-sided Student t test, with P

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Abnormalities of Mitral Subvalvular Apparatus in Hypertrophic Cardiomyopathy: Role of Intraoperative 3D Transesophageal Echocardiography.

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No abstract available

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US National Anesthesia Workload on Saturday and Sunday Mornings.

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BACKGROUND: In order to provide guidance to organizations considering elective weekend surgical case scheduling, we analyzed data from the American Society of Anesthesiologist's Anesthesia Quality Institute. We determined the US anesthesia workload on Saturdays and Sundays. METHODS: The American Society of Anesthesiologist's Anesthesia Quality Institute data were from all US anesthesia groups that submitted cases to the National Anesthesia Clinical Outcomes Registry for 2013. For each of the N = 2,075,188 cases, we identified the local date and time of the start of anesthesia care and the duration of anesthesia care. Anesthesia workload was measured as the time from the start to the end of continuous anesthesia care. Because elective cases are rarely scheduled on Sundays, we considered the difference in workload between Saturday and Sunday to estimate elective case scheduling. This difference would be an overestimate if some patients' scheduled cases were postponed from Friday to Saturday. Data are reported as mean +/- standard error; N = 13 four-week periods. RESULTS: The difference in the anesthesia minutes between Saturdays versus Sundays 7:00 AM to 2:59 PM (ie, elective caseload) represented just 0.38% +/- 0.02% of the total minutes nationwide; Saturday 1.57% +/- 0.03% versus Sunday 1.19% +/- 0.02%. The P

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Inhibition of Oxidative Stress in Renal Ischemia-Reperfusion Injury.

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BACKGROUND: Superoxide, nitric oxide (NO), and peroxynitrite are important mediators in the pathogenesis of ischemia-reperfusion (I/R) injury. We tested the renoprotective effects of allopurinol (ALP), a xanthine oxidase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), and 5,10,15,20-tetrakis (N-methyl-4-pyridyl) porphyrinato iron (III) (FeTMPyP) by selective inhibition of superoxide, NO, and peroxynitrite, respectively. METHODS: Male Sprague-Dawley rats were randomly assigned to 5 groups (n = 6 per group). Group 1 was a sham-operated group. Group 2 was the renal I/R group (30-minute ischemia followed by 24-hour reperfusion). Rats in groups 3, 4, and 5 received ALP, L-NAME, or FeTMPyP, respectively, at 5 minutes before the reperfusion. Serum creatinine (Cr), blood urea nitrogen (BUN), renal tissue malondialdehyde, superoxide dismutase, histological changes, apoptosis, and monocyte infiltration were evaluated. In addition, the combined treatment with ALP and L-NAME was compared with FeTMPyP in a second independent experiment. RESULTS: The administration of ALP, L-NAME, and FeTMPyP diminished the increase in Cr (P = .0066 for all) and BUN (P = .0066 for ALP; and P = .013 for L-NAME) induced by I/R injury and decreased the histological damage (P = .0066 for all). In addition, ALP, L-NAME, and FeTMPyP attenuated the oxidative stress response as determined by a decrease in malondialdehyde level (P = .0066 for all), apoptotic renal tubular cells (P = .0066 for all), and monocyte infiltration (P = .0066 for all). The combined treatment of ALP and L-NAME decreased Cr and BUN levels to a greater degree than FeTMPyP (P = .016 for Cr; P = .0079 for BUN). CONCLUSIONS: Superoxide, NO, and peroxynitrite are involved in renal I/R injury. The reduction of peroxynitrite formation, via inhibition of superoxide or NO, or the induction of peroxynitrite decomposition may be beneficial in renal I/R injury. (C) 2016 International Anesthesia Research Society

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Baseline Pulse Pressure, Acute Kidney Injury, and Mortality After Noncardiac Surgery.

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BACKGROUND: Increased pulse pressure (PP) is an important independent predictor of cardiovascular outcome and acute kidney injury (AKI) after cardiac surgery. The objective of this study was to determine whether elevated baseline PP is associated with postoperative AKI and 30-day mortality after noncardiac surgery. METHODS: We evaluated 9125 adult patients who underwent noncardiac surgery at Duke University Medical Center between January 2006 and December 2009. Baseline arterial blood pressure was defined as the mean of the first 5 measurements recorded by the automated record keeping system before inducing anesthesia. Multivariable logistic regression analysis was performed to determine whether baseline PP adjusted for other perioperative risk factors was independently associated with postoperative AKI and 30-day mortality. RESULTS: Of the 9125 patients, the baseline PP was 80 mm Hg in 773 (8.5%) patients. The incidence of AKI was 19.8%, which included 8.4% (151 patients) and 4.2% (76 patients) who experienced stage II and III AKI, respectively. In the risk-adjusted model for postoperative AKI, elevated baseline PP was associated with higher odds for postoperative AKI (adjusted odds ratio [OR] for every 20 mm Hg increase in PP, 1.17; 95% confidence interval [CI], 1.10-1.25; P

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Bruxism and dental implant failures: a multilevel mixed effects parametric survival analysis approach

Summary

Recent studies have suggested that the insertion of dental implants in patients being diagnosed with bruxism negatively affected the implant failure rates. The aim of the present study was to investigate the association between the bruxism and the risk of dental implant failure. This retrospective study is based on 2670 patients who received 10 096 implants at one specialist clinic. Implant- and patient-related data were collected. Descriptive statistics were used to describe the patients and implants. Multilevel mixed effects parametric survival analysis was used to test the association between bruxism and risk of implant failure adjusting for several potential confounders. Criteria from a recent international consensus (Lobbezoo et al., J Oral Rehabil, 40, 2013, 2) and from the International Classification of Sleep Disorders (International classification of sleep disorders, revised: diagnostic and coding manual, American Academy of Sleep Medicine, Chicago, 2014) were used to define and diagnose the condition. The number of implants with information available for all variables totalled 3549, placed in 994 patients, with 179 implants reported as failures. The implant failure rates were 13·0% (24/185) for bruxers and 4·6% (155/3364) for non-bruxers (P < 0·001). The statistical model showed that bruxism was a statistically significantly risk factor to implant failure (HR 3·396; 95% CI 1·314, 8·777; P = 0·012), as well as implant length, implant diameter, implant surface, bone quantity D in relation to quantity A, bone quality 4 in relation to quality 1 (Lekholm and Zarb classification), smoking and the intake of proton pump inhibitors. It is suggested that the bruxism may be associated with an increased risk of dental implant failure.



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Stable isotope tracers and exercise physiology: Past, present and future

Abstract

Stable isotope tracers have been invaluable assets in physiological research for over 80 years. The application of substrate-specific stable isotope tracers has permitted exquisite insight into amino acid, fatty-acid and carbohydrate metabolic regulation (i.e. incorporation, flux, oxidation, and in a tissue-specific and whole-body fashion) in health, disease and in response to acute and chronic exercise. Yet, despite many breakthroughs, there are limitations to "substrate specific" stable isotope tracers, which limit physiological insight e.g. the need for I.V infusions and restriction to short term studies (hours) in controlled laboratory settings. In recent years significant interest has developed in alternative stable isotope tracer techniques that overcome these limitations; in particular deuterium oxide (D2O or heavy water). The unique properties of this tracer mean that through oral administration, the turnover and flux through a number of different substrates (muscle proteins, lipids, glucose, DNA [satellite cells]) can be monitored simultaneously and flexibly (hours/weeks/months) without the need for restrictive experimental control. This makes it uniquely suited for the study of 'real world' human exercise physiology (amongst many other applications). Moreover, using D2O permits evaluation of turnover of plasma/muscle proteins (e.g. dynamic proteomics) in addition to metabolomics (e.g. fluxomics) to seek molecular underpinnings e.g. of exercise adaptation. Herein, we provide insight into the role of stable isotope tracers, from substrate-specific to novel D2O approaches, in facilitating our understanding of metabolism. Further novel potential applications of stable isotope tracers are also discussed in the context of integrating with the snowballing field of OMIC technologies.

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Pharmacogenetics of efavirenz discontinuation for reported central nervous system symptoms appears to differ by race

imageBackground: Efavirenz frequently causes central nervous system (CNS) symptoms. We evaluated genetic associations with efavirenz discontinuation for CNS symptoms within 12 months of treatment initiation. Methods: Patients had initiated efavirenz-containing regimens at an HIV primary care clinic in the Southeastern United States and had at least 12 months of follow-up data. Polymorphisms in CYP2B6 and CYP2A6 defined efavirenz metabolizer categories. Genome-wide genotyping enabled adjustment for population stratification. Results: Among 563 evaluable patients, 99 (17.5%) discontinued efavirenz within 12 months, 29 (5.1%) for CNS symptoms. The hazard ratio (HR) for efavirenz discontinuation for CNS symptoms in slow versus extensive metabolizers was 4.9 [95% confidence interval (CI): 1.9–12.4; P=0.001]. This HR in Whites was 6.5 (95% CI: 2.3–18.8; P=0.001) and 2.6 in Blacks (95% CI: 0.5–14.1; P=0.27). Considering only slow metabolizers, the HR in Whites versus Blacks was 3.1 (95% CI: 0.9–11.0; P=0.081). The positive predictive value of slow metabolizer genotypes for efavirenz discontinuation was 27% in Whites and 11% in Blacks. Conclusion: Slow metabolizer genotypes were associated significantly with efavirenz discontinuation for reported CNS symptoms. This association was considerably stronger in Whites than in Blacks.

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Impaired dacarbazine activation and 7-ethoxyresorufin deethylation in vitro by polymorphic variants of CYP1A1 and CYP1A2: implications for cancer therapy

imageObjectives: To extend our understanding of how interindividual variability mediates the efficacy of cancer treatment. Materials and methods: The kinetics of dacarbazine (DTIC) N-demethylation by the most frequent polymorphic variants of CYP1A1 (T461N, I462V) and CYP1A2 (F186L, D348N, I386F, R431W, R456H) were characterized, along with kinetic parameters for the O-deethylation of the prototypic CYP1A substrate 7-ethoxyresorufin, using recombinant protein expression and high-performance liquid chromatographic techniques. Results: A reduction of ∼30% in the catalytic efficiencies (measured as in-vitro intrinsic clearance, CLint) was observed for DTIC N-demethylation by the two CYP1A1 variants relative to wild type. Although a modest increase in the CLint value for DTIC N-demethylation was observed for the CYP1A2 D348N variant relative to the wild type, the CLint for the F186L variant was reduced and the I386F, R431W, and R456H variants all showed loss of catalytic function. Conclusion: Comparison of the kinetic data for DTIC N-demethylation and 7-ethoxyresorufin O-deethylation indicated that alterations in the kinetic parameters (Km, Vmax, CLint) observed with each of the CYP1A1 and CYP1A2 polymorphic variants were substrate dependent. These data indicate that cancer patients treated with DTIC who possess any of the CYP1A1-T461N and I462V variants or the CYP1A2-F186L, D348N, I386F, R431W, and R456H variants are likely to have decreased prodrug activation, and hence may respond less favorably to DTIC treatment compared with individuals with wild-type CYP1A alleles.

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A systematic analysis and comparison of warfarin initiation strategies

imageObjective: Randomized trials have reported inconsistent evidence on the effectiveness of algorithms that use genotypes to initiate warfarin therapy. The Clarification of Optimal Anticoagulation through Genetics (COAG) trial initiated therapy on the basis of predicted maintenance doses, with a pharmacogenetic-guided algorithm in one study group and a clinically guided algorithm in the other. The European Pharmacogenetics of Anticoagulant Therapy (EU-PACT) consortium initiated therapy on the basis of loading doses, with an algorithm-based prediction in one study group and a fixed-dose regimen in the other. To understand the differences between these trials, we compared the initial doses between alternative dosing algorithms (the pharmacogenetic-guided and clinically guided algorithms developed by Gage and colleagues and those developed by the International Warfarin Pharmacogenetics Consortium) and between the COAG and EU-PACT dose-initiation strategies. Methods: This was a secondary analysis of the COAG trial – a double-blind, randomized-controlled trial (2009–2013) – conducted at 18 clinical centers in the USA, which included 1010 adults initiating warfarin therapy, of whom 719 achieved maintenance dose. Results: Among COAG participants, the distribution of initial doses differed between algorithms, but showed similar prediction accuracy for maintenance dose. However, had the COAG trial implemented the EU-PACT strategy, the 3-day initial dose would have been 4.8 mg greater among participants randomized to pharmacogenetic-guided dosing, but only 2.5 mg greater among participants randomized to clinically guided dosing (P

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Influence of the CYP3A4/5 genetic score and ABCB1 polymorphisms on tacrolimus exposure and renal function in Brazilian kidney transplant patients

imageBackground: Polymorphisms in genes encoding transport proteins and metabolizing enzymes involved in tacrolimus (TAC) disposition may be important sources of individual variability during treatment. Objective: The aim of this study was to investigate the effect of combined CYP3A4 and CYP3A5 variants, using a CYP3A4/5 genetic score, and ABCB1 polymorphisms on therapeutic TAC monitoring and their relationship with clinical outcomes. Material and methods: Brazilian kidney transplant recipients (n=151), who received TAC over 3 months after transplantation, were genotyped for CYP3A4 rs2242480 (g.20230G>A), CYP3A5 rs15524 (g.31611C>T) and rs776746 (g.6986A>G), ABCB1 rs1128503 (c.1236C>T), rs1045642 (c.3435C>T), and rs2032582 (c.2677G>T/A) polymorphisms. Results: Frequencies of CYP3A4 g.20230A, CYP3A5 g.31611C, and g.6986A were 0.37, 0.26, and 0.28, respectively. These alleles were associated with TAC rapid metabolization and were used for CYP3A4/5 genetic score construction. A higher CYP3A4/5 genetic score was associated with higher TAC dose and lower concentrations for dose administered (Co/D, P

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β1-Adrenergic receptor Arg389Gly polymorphism affects the antiarrhythmic efficacy of flecainide in patients with coadministration of β-blockers

imageObjective: β1-Adrenergic receptor (β1-AR) stimulation modulates the antiarrhythmic activities of sodium channel blockers. The β1-AR Gly389 variant shows a marked decrease in agonist-stimulated cyclic AMP production compared with that of the wild-type Arg389 in vitro. We investigated whether the Arg389Gly polymorphism affects the efficacy of flecainide, a typical sodium channel blocker, in patients with or without coadministration of β-blockers. Methods: The effects of the β1-AR Arg389Gly polymorphism on the antiarrhythmic efficacy of flecainide were compared between with and without coadministered β-blockers in 159 patients with supraventricular tachyarrhythmia. The antiarrhythmic efficacy of flecainide was assessed for at least 2 months by evaluating symptomatology, 12-lead ECGs, and Holter monitoring results. Results: Genetic differences in the antiarrhythmic efficacy of flecainide were observed in patients with coadministration of β-blockers. Tachyarrhythmia was well controlled in 60% of Arg389-homozygotes, 30% of Gly389-heterozygotes, and 0% of Gly389-homozygotes (P=0.001). In contrast, no difference in the antiarrhythmic efficacy was observed among the three genotypes in the patients without coadministration of β-blockers (64, 70, and 60%, respectively). Heart rate in tachyarrhythmia in patients treated with flecainide was significantly higher in Gly389 carriers than in Arg389-homozygotes (P=0.013). Conclusion: The Gly389 polymorphism decreased the antiarrhythmic efficacy of flecainide when coadministered with β-blockers. The results indicate that the Arg389Gly polymorphism may play an important role in predicting the efficacy of flecainide in patients with coadministration of β-blockers.

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