Πέμπτη 19 Μαΐου 2016

Alcohol Breath Test: Gas Exchange Issues

The alcohol breath test is reviewed with a focus on gas exchange factors affecting its accuracy. The basis of the alcohol breath test is the assumption that alveolar air reaches the mouth during exhalation with no change in alcohol concentration. Recent investigations have shown that alcohol concentration is altered during its transit to the mouth. The exhaled alcohol concentration is modified by interaction with the mucosa of the pulmonary airways. Exhaled alcohol concentration is not an accurate indicator of alveolar alcohol concentration. Measuring alcohol concentration in the breath is very different process than measuring a blood level from air equilibrated with a blood sample. Airway exchange of alcohol leads to a bias against certain individuals depending on the anatomic and physiologic characteristics. Methodological modifications are proposed to improve the accuracy of the alcohol breath test to become fair to all.



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Separate and combined effects of a 10-d exposure to hypoxia and inactivity on oxidative function in vivo and mitochondrial respiration ex vivo in humans.

An integrative evaluation of oxidative metabolism was carried out in 9 healthy young men (age: 24.1±1.7 years [mean±SD]) prior to (CTRL) and following a 10-day horizontal bed rest, carried out in normoxia (N-BR) or hypoxia (FIO2=0.147; H-BR). H-BR was aimed to simulate planetary habitats. Pulmonary O2 uptake (V'O2) and vastus lateralis fractional O2 extraction (changes in deoxygenated hemoglobin+myoglobin concentration, [deoxy(Hb+Mb)]; near-infrared spectroscopy) were evaluated, in normoxia, during an incremental cycle ergometer exercise (CE) and one-leg knee extension exercise (KE) (aimed at reducing cardiovascular constraints to oxidative function). Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in permeabilized vastus lateralis fibers. During CE V'O2peak and [deoxy(Hb+Mb)]peak were lower (P<0.05) after both N-BR and H-BR vs. CTRL; during KE the variables were lower after N-BR, but not after H-BR. During CE the "overshoot" of [deoxy(Hb+Mb)] during constant work rate exercise was greater in N-BR and H-BR vs. CTRL, whereas during KE a significant difference vs. CTRL was observed only after N-BR. Maximal mitochondrial respiration determined ex vivo was not affected by both interventions. In N-BR, a significant impairment of oxidative metabolism occurred downstream of central cardiovascular O2 delivery and upstream of mitochondrial function, possibly at the level of the intramuscular matching between O2 supply and utilization (see the [deoxy(Hb+Mb)] overshoot) and peripheral O2 diffusion. Superposition of H on BR did not aggravate, and partially reversed, the impairment of muscle oxidative function in vivo induced by BR. The effects of longer exposures will have to be determined.



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Role of histidyl dipeptides in contractile function of fast and slow motor units in rat skeletal muscle

The physiological role of the muscle histidyl dipeptides carnosine and anserine in contractile function of various types of muscle fibres in vivo is poorly understood. Ten adult male Wistar rats were randomly assigned to two groups: control and supplemented for 10 weeks with beta-alanine, the precursor of carnosine (~640 mg/kg BW/day). Thereafter, contractile properties and fatigability of isolated fast fatigable (FF), fast resistant to fatigue (FR), and slow motor units (MUs) from the medial gastrocnemius were determined in deeply anaesthetized animals. The fatigue resistance was tested with a 40 Hz fatigue protocol followed by a second protocol at 40 Hz in fast and 20 Hz in slow units. In the supplemented rats, histidyl dipeptide concentrations significantly increased (P < 0.05) by 25% in the red portion of the gastrocnemius and carnosine increased by 94% in the white portion. The twitch force of FF units and maximum tetanic force of FR units were significantly increased (P < 0.05) and the half-relaxation time was prolonged in slow units (P < 0.05). FF units showed less fatigue during the first 10 s and FR units between 10 and 60 s during the 40 Hz fatigue test. In slow units, forces declined less during the first 60 s of the 20 Hz test. In conclusion, this in vivo experiment demonstrates that an elevation in muscle histidyl dipeptide content elicits beneficial changes in MU contractile characteristics and fatigue resistance. Carnosine and anserine seem to play an important yet divergent role in various MUs.



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Age-induced oxidative stress: How does it influence skeletal muscle quantity and quality?

With advancing age, skeletal muscle function declines as a result of strength loss. These strength deficits are largely due to reductions in muscle size (i.e., quantity) and its intrinsic force producing capacity (i.e., quality). Age-induced reductions in skeletal muscle quantity and quality can be the consequence of several factors, including accumulation of reactive oxygen and nitrogen species (ROS/RNS), also known as oxidative stress. In old muscle, oxidative stress has the potential to reduce muscle quantity by shifting protein balance in a deficit, and muscle quality by impairing activation at the neuromuscular junction, excitation-contraction (EC) coupling at the ryanodine receptor (RyR) and cross-bridge cycling within the myofibrillar apparatus. Of these, EC coupling failure mediated by RyR dysfunction via oxidation and/or nitrosylation appears to be the strongest candidate based on the publications reviewed. However, it is clear that age-associated oxidative stress has the ability to alter strength through several mechanisms and at various locations of the muscle fiber.



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How does an airway and subsequently the lung become hyperresponsive?

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Static and dynamic stress heterogeneity in a multiscale model of the asthmatic airway wall.

Airway hyper-responsiveness (AHR) is a key characteristic of asthma that remains poorly understood. Tidal breathing and deep inspiration ordinarily cause rapid relaxation of airway smooth muscle(ASM) (as demonstrated via application of length fluctuations to tissue strips) and are therefore implicated in modulation of AHR, but in some cases (such as application of transmural pressure oscillations to isolated intact airways) this mechanism fails. Here we use a multiscale biomechanical model for intact airways, that incorporates strain-stiffening due to collagen recruitment and dynamic force generation by ASM cells, to show that the geometry of the airway, together with interplay between dynamic active and passive forces, give rise to large stress and compliance heterogeneities across the airway wall that are absent in tissue strips. We show further that these stress heterogeneities result in auxotonic loading conditions that are currently not replicated in tissue-strip experiments; stresses in the strip are similar to hoop stress only at the outer airway wall and are under- or over-estimates of stresses at the lumen. Taken together these results suggest that a previously underappreciated factor - stress heterogeneities within the airway wall and consequent ASM cellular response to this micromechanical environment - could contribute to AHR and should be explored further both theoretically and experimentally.



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Exercise-induced endothelial progenitor cell mobilization is attenuated in impaired glucose tolerance and type 2 diabetes

Circulating endothelial progenitor cells (EPCs) contribute to vascular homeostasis and are fewer in those with type 2 diabetes mellitus (T2DM) compared with normal glucose tolerance (NGT), suggesting a link between EPCs and T2DM-associated vasculopathies. The purpose of this study was to assess EPC number and mobilization by acute submaximal exercise in older adults with NGT, impaired glucose tolerance (IGT) or T2DM. We tested the hypothesis that EPC mobilization is lower in IGT compared with NGT and further reduced in older adults with T2DM. Forty-five older (50-75 years of age) men and women with NGT (n=18), IGT (n=10), or T2DM (n=17) were characterized and underwent submaximal aerobic exercise tests with blood sampling for enumeration of vascular endothelial growth factor receptor 2+ (VEGFR2+) cells, CD34+ hematopoetic progenitor cells, and CD34+/VEGFR2+ EPCs by flow cytometry before and after exercise. Basal EPC number was 65% and 61% lower in the IGT and T2DM groups, respectively, compared with the NGT group (P<0.05). EPC number increased 23% after acute exercise in the NGT group (P<0.01), but did not change in the IGT or T2DMgroups. Before and after exercise, VEGFR2+ cell number was lower in a stepwise manner across the NGT, IGT and T2DM groups (P<0.05). Basal CD34+ cell number was lower in the IGT group compared with NGT (P<0.05), but did not change after exercise in any group. These findings suggest a CD34+/VEGFR2+ EPC mobilization defect in IGT and T2DM that could play a role in the cardiovascular diseases and capillary rarefaction associated with insulin resistance.



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Effects of hypervolemia by protein and glucose supplementation during aerobic training on thermal and arterial pressure regulations in hypertensive older men

The incidence of heat illness in older people has rapidly increased during midsummer for the last decade in Japan, and we suggested that whey-protein + carbohydrate supplementation during aerobic training increased plasma volume (PV) to enhance thermoregulatory adaptation in older men (J Appl Physiol, 107: 725-733, 2009); however, >60% of people age 65 and older suffer from hypertension and the symptoms may be worsened by the hypervolemia. To examine this, we randomly divided 21 older men (~69 years) with ~160 mmHg for systolic and ~90 mmHg for diastolic blood pressure at rest into two groups; Glc (N=11) consuming glucose alone (25g) and Pro-Glc (N=10) consuming whey-protein (10g) + glucose (15g), immediately after cycling exercise at 60-75% of peak aerobic capacity (VO2peak) for 60 min·day-1, 3 days·week-1, for 8 weeks. Before and after training, we measured PV (dye dilution), baroreflex sensitivity (BRS) of heart rate (Valsalva maneuver), and carotid arterial compliance (CAC) from carotid arterial diameter (ultrasound imaging) responses to pulsatile arterial pressure change (photoplethysmography) at rest. Additionally, we measured esophageal temperature (Tes) and forearm skin blood flow (plethysmography) during exercise at 60% pre-training VO2peak for 20 min in a warm environment. We found that the forearm skin vascular conductance response to increased Tes was enhanced in Pro-Glc with increased PV, but this was not found in Glc; however, despite the increased PV, arterial blood pressures rather decreased with increased CAC and BRS in Pro-Glc. Thus, the prescription was applicable to older men with hypertension to prevent heat illness during exercise.



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Pediatric perioperative adverse events requiring rapid response: a retrospective case–control study

Summary

Background

Perioperative pediatric adverse events have been challenging to study within and across institutions due to varying definitions, low event rates, and incomplete capture.

Aim

The aim of this study was to determine perioperative adverse event prevalence and to evaluate associated case characteristics and potential contributing factors at an academic pediatric quaternary-care center.

Methods

At the Children's Hospital of Philadelphia (CHOP), perioperative adverse events requiring rapid response assistance are termed Anesthesia Now (AN!) events. They have been accurately captured and entered into a quality improvement database since 2010. Adverse events involving open heart and cardiac catheterization cases are managed separately and not included in this database. We conducted a retrospective case–control study utilizing Compurecord (Phillips Healthcare, Andover, MA, USA), EPIC (EPIC, Verona, WI, USA), and Chartmaxx (MedPlus, Mason, OH, USA) systems matching AN! event cases to noncardiac controls (1 : 2) based on surgical date.

Results

From April 16, 2010 to September 25, 2012, we documented 213 AN! events in the noncardiac perioperative complex and remote sites at our main hospital. AN! prevalence was 0.0043 (1 : 234) with a 95% confidence interval (CI) (0.0037, 0.0049). Respiratory events, primarily laryngospasm, were most common followed by events of cardiovascular etiology. Median age was lower in the AN! group than in controls, 2.86 years (interquartile range 0.94, 10.1) vs 6.20 (2.85, 13.1), P < 0.0001. Odds ratios (with 95% CI) for age, 0.969 (0.941, 0.997); American Society of Anesthesiologists physical status, 1.67 (1.32, 2.12); multiple (≥2) services, 2.27 (1.13, 4.55); nonoperating room vs operating room location, 0.240 (0.133, 0.431); and attending anesthesiologist's experience, 0.976 (0.959, 0.992) were all significant.

Conclusions

Decreased age, increased comorbidities, multiple (vs single) surgical services, operating room (vs nonoperating room) location, and decreased staff experience were associated with increased risk of AN! events, which were predominantly respiratory in origin.

Thumbnail image of graphical abstract

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Comparison of anesthetic agents on otoacoustic emissions in children: propofol vs ketamine

Summary

Background

Otoacoustic emission (OAE) tests are important evaluation tools for diagnosis of peripheral auditory pathology. Sedation or general anesthesia may be required for the performance of the OAE tests. The aim of this retrospective study was to compare the effects of anesthetic agents, propofol and ketamine, on OAEs in children.

Methods

Fifty healthy children who underwent tonsillectomy and/or adenoidectomy under general anesthesia were included in this study. Three anesthesia induction protocols were defined for this study and the anesthesiologist applied his or her own choice. Transient evoked otoacoustic emissions (TEOAEs) and distortion-product otoacoustic emissions (DPOAEs) were automatically recorded in both ears of each patient prior to anesthetic (predrug) and following the loss of consciousness 5 min later (postdrug) by an audiologist blinded to the method of anesthesia. Acceptable TEOAEs were defined as signal noise ratio (S/N) of above 3 dB SPL (decibel sound pressure level) and DPOAEs of 6 dB SPL or above. Between-group and within-group comparisons and correlations were performed for statistical analysis.

Results

Retrospective review of the anesthesia charts from 44 cases that completed the study showed that propofol, ketamine, and sevoflurane induction protocols were used in 21, 18, and 5 cases, respectively. Measurements of 36 ears in the propofol group and 34 ears in the ketamine group were included in the final analysis. Postdrug TEOAE and DPOAE amplitudes were significantly lower than predrug amplitudes except at 8 kHz in the ketamine group. There was no significant statistical difference in postdrug DPOAE measurements between propofol and ketamine groups but a significant difference was observed at 2 and 3 kHz of postdrug TEOAE measurements. TEOAE measurements were below 3 dB in 8 of 34 ears after ketamine and in 1 of 36 ears after propofol administration. There was a significant difference between the groups with respect to the incidence of successful measurements of TEOAEs. The DPOAE measurements were affected less by these drugs.

Conclusion

DPOAE measurements were reduced similarly by propofol and ketamine anesthesia. Lower false outcome ratio in TEOAE measurements made propofol a better option than ketamine.

Thumbnail image of graphical abstract

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The presence of rapid on-site evaluation did not increase the adequacy and diagnostic accuracy of endoscopic ultrasound-guided tissue acquisition of solid pancreatic lesions with core needle

Abstract

Background

Rapid on-site evaluation (ROSE) improves the adequacy and accuracy of EUS-guided tissue acquisition, although it is not routinely widely available. Evidence suggested that core needles might overcome the absence of ROSE. The aim of this study was to evaluate the influence of ROSE on the adequacy and accuracy of EUS-guided tissue acquisition with core needles in patients with pancreatic solid lesions.

Methods

Patients who underwent EUS-guided tissue acquisition of pancreatic mass lesions were retrospectively identified at three tertiary referral centers and those performed with the core needle were included. Adequacy, defined as the rate of cases in which a tissue specimen for proper examination was achieved, with and without ROSE was the primary outcome measure. The diagnostic accuracy and tissue core acquisition were the secondary outcome measures.

Results

A total of 333 patients with pancreatic solid mass lesions were included in the study; 140 cases sampled with ROSE and 193 cases without ROSE. The adequacy was 92.1 % in the group sampled with ROSE and 88.1 % in the group without ROSE (p = 0.227). In the ROSE group sensitivity, specificity, and accuracy were 90.7, 100 and 92.1 %, respectively. In the group without ROSE, sensitivity, specificity, and accuracy were 87.2, 100, and 88.1 %, respectively. No difference for all these figures was observed between the two groups. The tissue core was available in 61.4 and 53.4 % of cases with and without ROSE, respectively (p = 0.143).

Conclusion

In the absence of ROSE, EUS-based tissue acquisition with Core needle should be considered since it achieves comparable tissue sampling adequacy and accuracy.



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The learning curve of laparoendoscopic single-site adrenalectomy: an analysis of over 100 cases

Abstract

Background

Recently, laparoendoscopic single-site adrenalectomy (LESS-A) has been developed as an alternative treatment for adrenal tumors. Although LESS-A is more technically complex than conventional laparoscopic adrenalectomy, its learning curve and the factors associated with poor surgical outcomes are poorly understood. We analyzed the learning curve of LESS-A and attempted to identify risk factors associated with worse surgical outcomes.

Methods

We identified 103 patients who underwent LESS-A [performed by the same surgeon (A.M.)] from 2009 to 2015. The learning curve was analyzed using the moving average method (the 10-case moving average), and we assessed potential risk factors for a prolonged pneumoperitoneum time.

Results

The learning curve stabilized at 30 cases. The cases were divided into two groups, the learning stage (LS) (cases 1–29) and master stage (MS) (cases 30–103) groups. The percentage of females and the frequency of previous abdominal surgery were higher in the LS group (p = 0.022 and 0.001, respectively). In the LS group, the mean pneumoperitoneum time was 92 ± 35 min, which was significantly longer than the equivalent value for the MS group (55 ± 18 min, p < 0.001). In the LS group, univariate analysis revealed that tumor size (≥50 mm) and the visceral fat area (VFA)/total fat area (TFA) ratio (≥0.49) were significantly associated with a prolonged pneumoperitoneum time (p = 0.046 and 0.046, respectively). In the multivariate analysis, tumor size and the VFA/TFA ratio were confirmed to be associated with a prolonged pneumoperitoneum time (p = 0.029 and 0.029, odds ratio 20.83 and 20.83, respectively). On the other hand, none of the examined factors were found to be associated with a prolonged pneumoperitoneum time in the MS group.

Conclusions

LESS-A was performed safely in most cases. However, surgeons who are learning the LESS-A procedure need to pay attention to tumor size and visceral obesity.



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Robotic surgery: current perceptions and the clinical evidence

Abstract

Background

It appears that a discrepancy exists between the perception of robotic-assisted surgery (RAS) and the current clinical evidence regarding robotic-assisted surgery among patients, healthcare providers, and hospital administrators. The purpose of this study was to assess whether or not such a discrepancy exists.

Methods

We administered survey questionnaires via face-to-face interviews with surgical patients (n = 101), healthcare providers (n = 58), and senior members of hospital administration (n = 6) at a community hospital that performs robotic surgery. The respondents were asked about their perception regarding the infection rate, operative time, operative blood loss, incision size, cost, length of hospital stay (LOS), risk of complications, precision and accuracy, tactile sensation, and technique of robotic-assisted surgery as compared with conventional laparoscopic surgery. We then performed a comprehensive literature review to assess whether or not these perceptions could be corroborated with clinical evidence.

Results

The majority of survey respondents perceived RAS as modality to decrease infection rate, increase operative time, decrease operative blood loss, smaller incision size, a shorter LOS, and a lower risk of complications, while increasing the cost. Respondents also believed that robotic surgery provides greater precision, accuracy, and tactile sensation, while improving intra-operative access to organs. A comprehensive literature review found little-to-no clinical evidence that supported the respondent's favorable perceptions of robotic surgery except for the increased costs, and precision and accuracy of the robotic-assisted technique.

Conclusions

There is a discrepancy between the perceptions of robotic surgery and the clinical evidence among patients, healthcare providers, and hospital administrators surveyed.



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Clinical benefits and oncologic equivalence of self-expandable metallic stent insertion for right-sided malignant colonic obstruction

Abstract

Background

The efficacy of stenting for right-sided malignant colonic obstruction is unknown. This study aimed to evaluate the safety, feasibility, and clinical benefits of self-expandable metallic stent insertion for right-sided malignant colonic obstruction.

Methods

Clinical data from patients who underwent right hemicolectomy for right colon cancer from January 2006 to July 2014 at three Korea University hospitals were retrospectively reviewed. A total of 39 patients who developed malignant obstruction in the right-sided colon were identified, and their data were analyzed.

Results

Stent insertion was attempted in 16 patients, and initial technical success was achieved in 14 patients (87.5 %). No stent-related immediate complications were reported. Complete relief from obstruction was achieved in all 14 patients. Twenty-five patients, including two patients who failed stenting, underwent emergency surgery. In the stent group, 93 % (13/14) of patients underwent elective laparoscopic surgery, and only one surgery was converted to an open procedure. All patients in the emergency group underwent emergency surgery within 24 h of admission. In the emergency group, only 12 % (3/25) of patients underwent laparoscopic surgery, with one surgery converted to an open procedure. All patients in both groups underwent either laparoscopy-assisted or open right/extended right hemicolectomy with primary anastomoses as the first operation. The operative times, retrieved lymph nodes, and pathologic stage did not differ between the two groups. Postoperative hospital stay (9.4 ± 3.4 days in the stent group vs. 12.4 ± 5.9 in the emergency group, p = 0.089) and time to resume oral food intake (3.2 ± 2.1 days in the stent group vs. 5.7 ± 3.4 in the emergency group, p = 0.019) were shorter in the stent group. And there were no significant differences in disease-free survival and overall survival between the two groups.

Conclusions

Stent insertion appears to be safe and feasible in patients with right-sided colonic malignant obstruction. It facilitates minimally invasive surgery and may result in better short-term surgical outcomes.



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A systematic review of low-cost laparoscopic simulators

Abstract

Background

Opportunities for surgical skills practice using high-fidelity simulation in the workplace are limited due to cost, time and geographical constraints, and accessibility to junior trainees. An alternative is needed to practise laparoscopic skills at home. Our objective was to undertake a systematic review of low-cost laparoscopic simulators.

Method

A systematic review was undertaken according to PRISMA guidelines. MEDLINE/EMBASE was searched for articles between 1990 and 2014. We included articles describing portable and low-cost laparoscopic simulators that were ready-made or suitable for assembly; articles not in English, with inadequate descriptions of the simulator, and costs >£1500 were excluded. Validation, equipment needed, cost, and ease of assembly were examined.

Results

Seventy-three unique simulators were identified (60 non-commercial, 13 commercial); 55 % (33) of non-commercial trainers were subject to at least one type of validation compared with 92 % (12) of commercial trainers. Commercial simulators had better face validation compared with non-commercial. The cost ranged from £3 to £216 for non-commercial and £60 to £1007 for commercial simulators. Key components of simulator construction were identified as abdominal cavity and wall, port site, light source, visualisation, and camera monitor. Laptop computers were prerequisite where direct vision was not used. Non-commercial models commonly utilised retail off-the-shelf components, which allowed reduction in costs and greater ease of construction.

Conclusion

The models described provide simple and affordable options for self-assembly, although a significant proportion have not been subject to any validation. Portable simulators may be the most equitable solution to allow regular basic skills practice (e.g. suturing, knot-tying) for junior surgical trainees.



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Improving training of laparoscopic tissue manipulation skills using various visual force feedback types

Abstract

Background

Visual force feedback allows trainees to learn laparoscopic tissue manipulation skills. The aim of this experimental study was to find the most efficient visual force feedback method to acquire these skills. Retention and transfer validity to an untrained task were assessed.

Methods

Medical students without prior experience in laparoscopy were randomized in three groups: Constant Force Feedback (CFF) (N = 17), Bandwidth Force Feedback (BFF) (N = 16) and Fade-in Force Feedback (N = 18). All participants performed a pretest, training, post-test and follow-up test. The study involved two dissimilar tissue manipulation tasks, one for training and one to assess transferability. Participants performed six trials of the training task. A force platform was used to record several force parameters.

Results

A paired-sample t test showed overall lower force parameter outcomes in the post-test compared to the pretest (p < .001). A week later, the force parameter outcomes were still significantly lower than found in the pretest (p < .005). Participants also performed the transfer task in the post-test (p < .02) and follow-up (p < .05) test with lower force parameter outcomes compared to the pretest. A one-way MANOVA indicated that in the post-test the CFF group applied 50 % less Mean Absolute Nonzero Force (p = .005) than the BFF group.

Conclusion

All visual force feedback methods showed to be effective in decreasing tissue manipulation force as no major differences were found between groups in the post and follow-up trials. The BFF method is preferred for it respects individual progress and minimizes distraction.



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A systematic review of community based hepatitis C treatment

BMC Infectious Diseases

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On-treatment HCV RNA as a predictor of sustained virologic response in HCV genotype 3–infected patients treated with daclatasvir and sofosbuvir

Liver International

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Hepatitis B virus expression and replication in ovum and the influencing factors

Saudi Journal of Gastroenterology

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A phase II study of a modified FOLFOX6 regimen as neoadjuvant chemotherapy for locally advanced gastric cancer

British Journal of Cancer

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Preclinical development of Ramizol, an antibiotic belonging to a new class, for the treatment of Clostridium difficile colitis

The Journal of Antibiotics

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Efficacy of double-coated probiotics for irritable bowel syndrome: a randomized double-blind controlled trial

Journal of Gastroenterology

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Intensity of adjuvant chemotherapy regimens and grade III–V toxicities among elderly stage III colon cancer patients

European Journal of Cancer

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Design of a multicentre randomized controlled trial to evaluate the effectiveness of a tailored clinical support intervention to enhance return to work for gastrointestinal cancer patients

BMC Cancer

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An open-label randomized control study to compare the efficacy of vitamin E versus ursodeoxycholic acid in nondiabetic and noncirrhotic Indian NAFLD patients

Saudi Journal of Gastroenterology

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Appropriateness of testing for anti-tumor necrosis factor agent and antibody concentrations, and interpretation of results

Clinical Gastroenterology and Hepatology

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Full-length LGR5-positive cells have chemoresistant characteristics in colorectal cancer

British Journal of Cancer

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Dual-priming oligonucleotide-based multiplex PCR using tissue samples from the rapid urease test kit for the detection of Helicobacter pylori in bleeding peptic ulcers

Digestive and Liver Diseases

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Ferric maltol in iron deficiency anaemia in patients with inflammatory bowel disease

Drugs & Therapy Perspectives

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Risk of advanced neoplasia in first-degree relatives with colorectal cancer: a large multicenter cross-sectional study

PLoS Medicine

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Increased IL-17A/IL-17F expression ratio represents the key mucosal T helper/regulatory cell-related gene signature paralleling disease activity in ulcerative colitis

Journal of Gastroenterology

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Dietary total antioxidant capacity and pancreatic cancer risk: an Italian case–control study

British Journal of Cancer

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Resistance analyses of japanese hepatitis c-infected patients receiving sofosbuvir or ledipasvir/sofosbuvir containing regimens in phase 3 studies

Journal of Viral Hepatitis

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Randomized clinical trial comparing ten day concomitant and sequential therapies for Helicobacter pylori eradication in a high clarithromycin resistance area

European Journal of Internal Medicine

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A model to identify sarcopenia in patients with cirrhosis

Clinical Gastroenterology and Hepatology

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Outcome of acute upper gastrointestinal bleeding in patients with coronary artery disease: A matched case–control study

Saudi Journal of Gastroenterology

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Issue Information - Editorial Board



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Predicting the Best Fit: A Comparison of Response Surface Models for Midazolam and Alfentanil Sedation in Procedures with Varying Stimulation.

BACKGROUND: Selecting an effective dose of sedative drugs in combined upper and lower gastrointestinal endoscopy is complicated by varying degrees of pain stimulation. We tested the ability of 5 response surface models to predict depth of sedation after administration of midazolam and alfentanil in this complex model. The procedure was divided into 3 phases: esophagogastroduodenoscopy (EGD), colonoscopy, and the time interval between the 2 (intersession). METHODS: The depth of sedation in 33 adult patients was monitored by Observer Assessment of Alertness/Scores. A total of 218 combinations of midazolam and alfentanil effect-site concentrations derived from pharmacokinetic models were used to test 5 response surface models in each of the 3 phases of endoscopy. Model fit was evaluated with objective function value, corrected Akaike Information Criterion (AICc), and Spearman ranked correlation. A model was arbitrarily defined as accurate if the predicted probability is

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Hemostatic Therapy Using Tranexamic Acid and Coagulation Factor Concentrates in a Model of Traumatic Liver Injury.

BACKGROUND: The potential clinical benefits of targeted therapy with coagulation factor concentrates (e.g., fibrinogen) and antifibrinolytic agents (e.g., tranexamic acid [TXA]) for the treatment of trauma-induced coagulopathy are increasingly recognized. We hypothesized that human fibrinogen concentrate (FC) and prothrombin complex concentrate (PCC), administered as combined therapy with TXA, would provide additive effects for reducing blood loss in an animal trauma model. METHODS: Thirty-six pigs were subjected to 2 consecutive blunt liver injuries, resulting in severe hemorrhagic shock and coagulopathy. Intervention comprised saline (control group); TXA (15 mg kg-1, TXA group); TXA and FC (90 mg kg-1, TXA-FC); or TXA, FC, and PCC (20 U kg-1, TXA-FC-PCC). Blood loss, thromboelastometry (ROTEM), measures of thrombin generation, platelet activation, and global coagulation variables were monitored for 4 hours. Tissue sections were examined to determine the occurrence of thromboembolic events. RESULTS: Total blood loss was similar in the TXA-FC and TXA-FC-PCC groups (mean +/- SD: 1012 +/- 86 mL and 1037 +/- 118 mL, respectively; P = 1.000). These values were both lower (P

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The Enigma of Postoperative Troponin Elevation.

No abstract available

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Transcriptomic Analysis of Differentially Expressed Genes During Larval Development of Rapana venosa by Digital Gene Expression Profiling

During the life cycle of shellfish, larval development, especially metamorphosis, has a vital influence on the dynamics, distribution and recruitment of natural populations, as well as seed breeding. Rapana venosa, a carnivorous gastropod, is an important commercial shellfish in China and is an ecological invader in the USA, Argentina and France. However, information about the mechanism of its early development is still limited, because research in this area has long suffered from a lack of genomic resources. In this study, fifteen digital gene expression (DGE) libraries from five developmental stages of R. venosa were constructed and sequenced on the IIIumina Hi-Seq 2500 platform. Bioinformatics analysis identified numerous differentially and specifically expressed genes which revealed some genes associated with growth, nervous system, digestive system, immune system and apoptosis participate in important developmental processes. The functional analysis of differentially expressed genes was further implemented by gene ontology and Kyoto encyclopedia of genes and genomes enrichment. DGE profiling provided a general picture of the transcriptomic activities during the early development of R. venosa, which may provide interesting hints for further study. Our data represent the first comparative transcriptomic information available for the early development of R. venosa, which is a prerequisite for better understanding the physiological traits controlling development.



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ForestPMPlot: A Flexible Tool for Visualizing Heterogeneity between Studies in Meta-analysis

Meta-analysis has become a popular tool for genetic association studies to combine derent genetic studies. A key challenge in meta-analysis is heterogeneity or the derences in eect sizes between studies. Heterogeneity complicates the interpretation of meta-analyses. In this paper, we describe ForestPMPlot, a flexible visualization tool for analyzing studies included in a meta-analysis. The main feature of the tool is visualizing the derences in the eect sizes of the studies to understand why the studies exhibit heterogeneity for a particular phenotype and locus pair under derent conditions. We show the application of this tool to interpret a meta-analysis of 17 mouse studies and to interpret a multi-tissue eQTL study.



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The Rate and Spectrum of Spontaneous Mutations in Mycobacterium smegmatis, a Bacterium Naturally Devoid of the Post-replicative Mismatch Repair Pathway

Mycobacterium smegmatis is a bacterium that is naturally devoid of known post-replicative DNA mismatch repair (MMR) homologs, mutS and mutL, providing an opportunity to investigate how the mutation rate and spectrum has evolved in the absence of a highly-conserved primary repair pathway. Mutation accumulation experiments of M. smegmatis yielded a base-substitution mutation rate of 5.27 x 10-10 per site per generation, or 0.0036 per genome per generation, which is surprisingly similar to the mutation rate in MMR-functional unicellular organisms. Transitions were found more frequently than transversions, with the A:T -> G:C transition rate significantly higher than the G:C -> A:T transition rate, opposite to what is observed in most studied bacteria. We also found that the transition-mutation rate of M. smegmatis is significantly lower than that of other naturally MMR-devoid or MMR-knockout organisms. Two possible candidates that could be responsible for maintaining high DNA fidelity in this MMR-deficient organism are the ancestral-like DNA polymerase DnaE1, which contains a highly efficient DNA proofreading histidinol phosphatase (PHP) domain, and/or the existence of a Uracil-DNA glycosylase B (UdgB) homolog that might protect the GC-rich M. smegmatis genome against DNA damage arising from oxidation or deamination. Our results suggest that M. smegmatis has a non-canonical Dam (DNA adenine methylase) methylation system, with target motifs differing from those previously reported. The mutation features of M. smegmatis provide further evidence that genomes harbor alternative routes for improving replication fidelity even in the absence of major repair pathways.



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Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients

Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here we describe the characterization of a multi-incident MS family which nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients and 886 controls from Canada identified ten additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports co-segregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients and 8797 controls from Canada, France, Spain, Germany, Belgium and Austria failed to identify significant association with disease (p=0.117), despite an overall higher prevalence in patients (OR=1.32; 95% CI=0.93-1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility.



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Homeobox Is Pivotal for OsWUS Controlling Tiller Development and Female Fertility in Rice

OsWUS has recently been shown to be a transcription factor gene critical for tiller development and fertility in rice. The OsWUS protein consists of three conserved structural domains, but their biological functions are still unclear. We discovered a new rice mutant resulting from tissue culture, which hardly produced tillers and exhibited complete female sterility. The male and female floral organs of the mutant were morphologically indistinguishable from those of the wild type. We named the mutant srt1 for completely sterile and reduced tillering 1. Map-based cloning revealed that the mutant phenotypes were caused by a mutation in OsWUS. Compared with the two previously reported null allelic mutants of OsWUS (tab1-1 and moc3-1), which could produce partial N-terminal peptides of OsWUS, the srt1 protein contained a deletion of only seven amino acids within the conserved homeobox domain of OsWUS. However, the mutant phenotypes (monoculm and female sterility) displayed in srt1 were as typical and severe as those in tab1-1 and moc3-1. This indicates that the homeobox domain of SRT1 is essential for the regulation of tillering and sterility in rice. In addition, srt1 showed an opposite effect on panicle development to that of the two null allelic mutants, implying that the srt1 protein might still have partial or even new functions on panicle development. The results of this study suggest that the homeobox domain is pivotal for OsWUS function.



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An Improved Binary Vector and Escherichia coli strain for Agrobacterium tumefaciens-Mediated Plant Transformation

The plasmid vector pGreenII is widely used to produce plant transformants via a process that involves propagation in Escherichia coli. However, we show here that pGreenII-based constructs can be unstable in E. coli as a consequence of them hampering cell division and promoting cell death. In addition, we describe a new version of pGreenII that does not cause these effects, thereby removing the selective pressure for mutation, and a new strain of E. coli that better tolerates existing pGreenII-based constructs without reducing plasmid yield. The adoption of the new derivative of pGreenII and E. coli strain, which we have named pViridis and MW906 respectively, should help to ensure the integrity of genes destined for study in plants, while they are propagated and manipulated in E. coli. The mechanism by which pGreenII perturbs E. coli growth appears to be dysregulation within the ColE1 origin of replication.



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Construction and Annotation of a High Density SNP Linkage Map of the Atlantic Salmon (Salmo salar) Genome

Background: High density linkage maps are useful tools for fine-scale mapping of quantitative trait loci, and characterisation of the recombination landscape of a species' genome. Genomic resources for Atlantic salmon (Salmo salar) include a well-assembled reference genome and high density SNP arrays. Our aim was to create a high density linkage map, and to align it with the reference genome assembly. Results: Over 96 K SNPs were mapped and ordered on the 29 salmon linkage groups using a pedigreed population comprising 622 fish from 60 nuclear families, all genotyped with the 'ssalar01' high density SNP array. The number of SNPs per group showed a high positive correlation with physical chromosome length (r = 0.95). While the order of markers on the genetic and physical maps was generally consistent, areas of discrepancy were identified. Approximately 6.5 % of the previously unmapped reference genome sequence was assigned to chromosomes using the linkage map. Male recombination rate was lower than females across the vast majority of the genome, but with a notable peak in sub-telomeric regions. Finally, using RNA-Seq data to annotate the reference genome, the mapped SNPs were categorised according to their predicted function, including annotation of ~ 2.5 K putative non-synonymous variants. Conclusions: The highest density SNP linkage map for any salmonid species has been created, annotated, and integrated with the Atlantic salmon reference genome assembly. This map highlights the marked heterochiasmy of salmon, and provides a useful 36 resource for salmonid genetics and genomics research.



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Using Genotyping by Sequencing To Map Two Novel Anthracnose Resistance Loci in Sorghum bicolor

Colletotrichum sublineola is an aggressive fungal pathogen that causes anthracnose in sorghum (Sorghum bicolor (L.) Moench). The obvious symptoms of anthracnose are leaf blight and stem rot. Sorghum, the fifth most widely grown cereal crop in the world, can be highly susceptible to the disease, most notably in hot and humid environments. In the southeastern United States the acreage of sorghum has been increasing steadily in recent years, spurred by growing interest in producing biofuels, bio-based products, and animal feed. Resistance to anthracnose is, therefore, of paramount importance for successful sorghum production in this region. To identify anthracnose resistance loci present in the highly resistant cultivar 'Bk7', a biparental mapping population of F3:4 and F4:5 sorghum lines was generated by crossing 'Bk7' with the susceptible inbred 'Early Hegari-Sart'. Lines were phenotyped in three environments and two years following natural infection. The population was genotyped by sequencing. Following a stringent custom filtering protocol, a total of 5,186 and 2,759 informative SNP markers were identified in the two populations. Segregation data and association analysis identified resistance loci on chromosomes 7 and 9, with the resistance alleles derived from 'Bk7'. Both loci contain multiple classes of defense-related genes based on sequence similarity and gene ontologies. Genetic analysis following an independent selection experiment of lines derived from a cross between 'Bk7' and sweet sorghum 'Mer81-4' narrowed the resistance locus on chromosome 9 substantially, validating this QTL. As observed in other species, sorghum appears to have regions of clustered resistance genes. Further characterization of these regions will facilitate the development of novel germplasm with resistance to anthracnose and other diseases.



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Comparative Genomics of a Parthenogenesis-Inducing Wolbachia Symbiont

Wolbachia is an intracellular symbiont of invertebrates responsible for inducing a wide variety of phenotypes in its host. These host-Wolbachia relationships span the continuum from reproductive parasitism to obligate mutualism, and provide a unique system to study genomic changes associated with the evolution of symbiosis. We present the genome sequence from a parthenogenesis-inducing Wolbachia strain (wTpre) infecting the minute parasitoid wasp Trichogramma pretiosum. The wTpre genome is the most complete parthenogenesis-inducing Wolbachia genome available to date. We use comparative genomics across 16 Wolbachia strains, representing five supergroups, to identify a core Wolbachia genome of 496 sets of orthologous genes. Only 14 of these sets are unique to Wolbachia when compared to other bacteria from the Rickettsiales. We show that the B-supergroup of Wolbachia, of which wTpre is a member, contains a significantly higher number of ankyrin repeat-containing genes than other supergroups. In the wTpre genome, there is evidence for truncation of the protein coding sequences in 20% of open reading frames, mostly as a result of frameshift mutations. The wTpre strain represents a conversion from cytoplasmic incompatibility to a parthenogenesis-inducing lifestyle, and is required for reproduction in the Trichogramma host it infects. We hypothesize that the large number of coding frame truncations has accompanied the change in reproductive mode of the wTpre strain.



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Gender difference in career advancement and job satisfaction in anaesthesia: A cross-sectional study.

No abstract available

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Effects of remifentanil on pharyngeal swallowing: A double blind randomised cross-over study in healthy volunteers.

BACKGROUND: Exposure to remifentanil increases the incidence of pulmonary aspiration in healthy volunteers. This effect may be explained by impairment of airway defence mechanisms and/or altered swallowing function. Pressure-flow analysis is a technique that allows objective assessment of swallowing based on pressure-impedance patterns recorded during bolus swallowing. OBJECTIVES: The aim of this study was to use pressure-flow analysis to quantify the effect of remifentanil on healthy pharyngeal swallowing and to compare these effects with morphine. DESIGN: A double-blind, randomised, cross-over study. SETTING: A tertiary care teaching hospital. VOLUNTEERS: Eleven young volunteers (mean age, 23 years) and seven older volunteers (mean age, 73 years). INTERVENTIONS: Volunteers were studied twice and received either a target-controlled remifentanil infusion (target concentrations: young, 3 ng ml-1; old, 2 ng ml-1) or a bolus injection of morphine (dose: young, 0.1 mg kg-1; old, 0.07 mg kg-1). Pharyngeal pressure and impedance were recorded with an indwelling catheter while swallowing 10 boluses of liquid during each measuring phase. Variables defining swallowing function were calculated and compared to determine drug effects. MAIN OUTCOME MEASURES: Pharyngeal pressure-flow variables following remifentanil exposure. RESULTS: Changes produced by remifentanil in the measured variables were consistent with greater dysfunction of swallowing. Both the strength of the pharyngeal contractions and pharyngeal bolus propulsion were reduced, whereas flow resistance was increased. The swallow risk index, a global index of swallowing dysfunction, increased overall. At the experimental doses tested, morphine produced similar, but less extensive effects on swallowing. CONCLUSION: Remifentanil induced dysfunction of the pharyngeal swallowing mechanism. This may contribute to an increased risk of aspiration. TRIAL REGISTRATION: NCT01924234 ( http://ift.tt/PmpYKN). (C) 2016 European Society of Anaesthesiology

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Reply to: are transdermal opioids contraindicated in patients at risk of suicide?.

No abstract available

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