The effect of fentanyl coadministration on sneezing during nasal local anesthetic injection for plastic surgery under propofol-based intravenous sedation: A retrospective case-controlled study.

BACKGROUND: Injection of local anesthetic for surgical procedures on the skin of the nose under intravenous sedation can provoke sneezing, which can be hazardous to the patient, surgeon, and other staff. Yet, there is little information on factors that influence sneezing under these circumstances. The aim of our study was to investigate the influence of adding fentanyl to propofol-based sedation on the incidence of sneezing during local anesthetic injection on the nose for plastic surgery. METHODS: A retrospective chart review was conducted on 32 patients who had undergone plastic surgery procedures on the nose under local anesthetic with intravenous sedation. RESULTS: Twenty-two patients received fentanyl in addition to propofol. Of these, only two patients sneezed (9.1 percent). In contrast, nine out of the 10 patients who did not receive fentanyl sneezed (90 percent). This included two patients who had received midazolam and propofol. CONCLUSIONS: These findings indicate that there was a high rate of sneezing during nasal local anesthetic injections performed under propofol-based intravenous sedation, unless the sedation was supplemented with fentanyl. We now recommend the coadministration of fentanyl during nasal local anesthetic injections under propofol-based sedation. Further studies are required to determine whether this observation is related to the depth of sedation alone, or whether the reduction in sneezing is related to the coadministration of an opioid. Further studies should also investigate potential side effects of coadministration of fentanyl or other opioids.

Acute Airway Obstruction from Megaoesophagus Secondary to Achalasia Evaluated with Flexible Bronchoscope.

A 94-year-old female presented to the emergency department with acute expiratory stridor. In the absence of an otorhinolaryngologist, an urgent laryngoscopy was performed using a flexible bronchoscope by an anaesthesiologist in the emergency department leading to a change in management. Subsequent radiographs confirmed severe tracheal compression from megaoesophagus secondary to achalasia as the cause of acute airway obstruction. Use of flexible bronchoscope as a diagnostic tool by an anaesthesiologist to evaluate a patient presenting with signs of acute airway obstruction may lead to a safer and more careful airway management planning. Suggestions are also made regarding establishment of emergency surgical airways when conventional approaches fail.

The Impact of Earplugs and Eye Masks on Sleep Quality in Surgical ICU Patients at Risk for Frequent Awakenings.

OBJECTIVES: Sleep disturbances may contribute to the development of delirium, prolonged ICU stay, and increased mortality. There is conflicting data on the effectiveness of earplugs and eye masks for sleep promotion in the ICU. This study evaluates the impact of earplugs and eye masks on sleep quality in postoperative surgical ICU patients at risk for frequent awakenings. DESIGN: Prospective randomized controlled trial. SETTING: Surgical ICU within the University of Texas Southwestern Medical Center. PATIENTS: Adult, female patients admitted to the surgical ICU requiring hourly postoperative assessments following breast free flap surgery between February 2018 and October 2019. INTERVENTIONS: Patients were randomized into an intervention group or a control group. The intervention group received earplugs and eye masks in addition to standard postoperative care, whereas the control group received standard postoperative care. MEASUREMENTS AND MAIN RESULTS: The primary outcome was overall sleep quality assessed via the Richards-Campbell Sleep Questionnaire. Secondary outcomes of patient satisfaction and rates of ICU delirium were assessed with a modified version of the Family Satisfaction in the ICU survey and the Confusion Assessment Method for the ICU. After a planned interim analysis, the study was stopped early because prespecified criteria for significance were attained. Compared with the control group's average Richards-Campbell Sleep Questionnaire total score of 47.3 (95% CI, 40.8-53.8), the intervention group's average Richards-Campbell Sleep Questionnaire total score was significantly higher at 64.5 (95% CI, 58.3-70.7; p = 0.0007). There were no significant between-group differences for Confusion Assessment Method for the ICU scores or modified Family Satisfaction in the ICU survey scores. CONCLUSIONS: These results suggest that earplugs and eye masks are effective in improving sleep quality in ICU patients undergoing frequent assessments. The results strengthen the evidence for nonpharmacologic sleep-promoting adjuncts in the ICU.

Pulmonary aspiration during procedural sedation for colonoscopy resulting from positional change managed without oral endotracheal intubation.

BACKGROUND: Pulmonary aspiration under anaesthesia is a feared complication. It is likely that the incidence of aspiration occurring during procedural sedation is underreported; although rare, fatalities do occur. The supine position increases the risk of pulmonary aspiration in gastrointestinal endoscopy during procedural sedation. Immediate oral endotracheal intubation has traditionally been the cornerstone of management for aspiration during anaesthesia; however, this may not be always beneficial when aspiration occurs during procedural sedation. To my knowledge, this is the first case report of aspiration pneumonitis resulting from surgical repositioning during colonoscopy under procedural sedation. CASE PRESENTATION: A 72-year-old female underwent elective outpatient diagnostic colonoscopy. Intravenous propofol infusion was commenced for the procedural sedation. A large amount of non-particulate vomitus was expelled from the oropharynx as the patient was repositioned from the left lateral to supine position. Oxygen saturation on pulse oximetry immediately dropped to below 90% during the event. The patient was managed successfully without oral endotracheal intubation. CONCLUSIONS: Anaesthesiologists need to be mindful of factors that raise the risk of aspiration during procedural sedation. Gastrointestinal endoscopy poses a higher risk of aspiration than other procedures, and positional change may be a precipitant. Aspiration that occurs during procedural sedation may be more safely managed by avoiding immediate oral endotracheal intubation.

MR elastography of the liver: comparison of three measurement methods.

AIM: To analyse the inter- and intra-observer agreement of liver stiffness value (LSV) using three methods with 3 T magnetic resonance elastography (MRE) and to investigate factors related to LSV difference. MATERIALS AND METHODS: This retrospective study included 147 patients. Two independent observers measured the LSV using three region of interest (ROI) methods: (1) circular ROI with a radius of 1 cm in the right lobe, (2) largest ROI possible, and (3) average value considering the measurement area. The agreement and factors related to difference of LSV were investigated. RESULTS: The intraclass correlation coefficients were excellent at 0.982-0.997 in all methods. The differences between observers for method 1 were significantly larger than those of method 2 or method 3 (p<0.001). The Child-Pugh classification was only related to LSV difference (p<0.001). CONCLUSION: Methods 2 and 3 were significantly more reliable than method 1. The Child-Pugh classification was only related to difference of LSV.

Some Possibilities to Study New Prophylactics against Nerve Agents.

Nerve agents belong to the most dangerous chemical warfare agents and can be/were misused by terrorists. Effective prophylaxis and treatment is necessary to diminish their effect. General principles of prophylaxis are summarized (protection against acetylcholinesterase inhibition, detoxification, treatment "in advance" and use of different drugs). They are based on the knowledge of mechanism of action of nerve agents. Among different examinations, it is necessary to test prophylactic effectivity in vivo and compare the results with protection in vitro. Chemical and biological approaches to the development of new prophylactics would be applied simultaneously during this research. Though the number of possible prophylactics is relatively high, the only four drugs were introduced into military medical practice. At present, pyridostigmine seems to be common prophylactic antidote; prophylactics panpal (tablets with pyridostigmine, trihexyphenidyl and benactyzine), transant (transdermal patch containing HI-6) are other means introduced into different armies as prophylactics. Scavenger commercionally available is Protexia®. Future development will be focused on scavengers, and on other drugs either reversible cholinesterase inhibitors (e.g., huperzine A, gallantamine, physostigmine, acridine derivatives) or other compounds.

Oxidative stress induced by oxime reactivators of acetylcholinesterase in vitro.

In this study, we determined the effect of methoxime (MMB-4), asoxime (HI-6), obidoxime (LüH-6), trimedoxime (TMB-4), and pralidoxime (2-PAM) on redox homeostasis in vitro. Cultured human hepatoma cells (HepG2) were exposed to oximes at concentrations equivalent to their IC50 (assessed using MTT assay) and evaluated 1, 4 and 24 h after incubation. Additionally, intact, early and late apoptotic and necrotic cells were quantified by microcapillary flow cytometry. Intracellular levels of oxygen/nitrogen species were determined using two fluorescent probes (2',7'-dichlorodihydrofluorescein diacetate and dihydroethidium). Malondialdehyde and 3-nitrotyrosine were measured by LC-MS/MS. Non-protein thiols and non-protein disulfides were evaluated using HPLC-UV to reflect antioxidant capacity. Oxidative and nitrosative stress was induced by LüH-6, TMB-4 and MMB-4, whereas 2-PAM and HI-6 appeared as weak oxidative stressors with no activity towards nitrosative stress in HepG2 cells. Based on these results, bisquartenary oxime reactivators containing two functional oxime groups at the position 4 of pyridinium ring appear as more intense oxidative and nitrosative inducers. Activation of apoptosis and necrosis do not seem to correlate with generation of RONS. On the other hand, both processes rather reflect MDA concentrations, i.e. the damage of biomolecules.

Anti-viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus-related hepatocellular carcinoma: real-world east and west experience.

BACKGROUND: Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti-viral therapy affects survival after HCC diagnosis. METHODS: This was an international multicentre cohort study of 2518 HBV-related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti-viral therapy and cirrhosis on patients' risk of death. RESULTS: Approximately, 48% of patients received anti-viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti-viral therapy would have been indicated for >60% of the patients not on anti-viral therapy based on American criteria. Patients with cirrhosis had lower 5-year survival (34% vs 46%; P < 0.001) while patients receiving anti-viral therapy had increased 5-year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti-viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001). CONCLUSIONS: Anti-viral therapy improved overall survival in patients with HBV-related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti-viral therapy in HBV-related HCC and better linkage-to-care for HBV patients are needed.

In vivo assembly of a truncated H subunit mutant of the Rhodobacter sphaeroides photosynthetic reaction centre and direct electron transfer from the QA quinone to an electrode.

We address a challenge in the engineering of proteins to redirect electron transfer pathways, using the bacterial photosynthetic reaction centre (RC) pigment-protein complex. Direct electron transfer is shown to occur from the QA quinone of the Rhodobacter sphaeroides RC containing a truncated H protein and bound on the quinone side to a gold electrode. In previous reports of binding to the quinone side of the RC, electron transfer has relied on the use of a soluble mediator between the RC and an electrode, in part because the probability of QB quinone reduction is much greater than that of direct electron transfer through the large cytoplasmic domain of the H subunit, presenting a ~ 25 Å barrier. A series of C-terminal truncations of the H subunit were created to expose the quinone region of the RC L and M proteins, and all truncated RC H mutants assembled in vivo. The 45M mutant was designed to contain only the N-terminal 45 amino acid residues of the H subunit including the membrane-spanning α-helix; the mutant RC was stable when purified using the detergent N-dodecyl-ß-D-maltoside, contained a near-native ratio of bacteriochlorophylls to bacteriopheophytins, and showed a charge-separated state of [Formula: see text]. The 45M-M229 mutant RC had a Cys residue introduced in the vicinity of the QA quinone on the newly exposed protein surface for electrode attachment, decreasing the distance between the quinone and electrode to ~ 12 Å. Steady-state photocurrents of up to around 200 nA/cm2 were generated in the presence of 20 mM hydroquinone as the electron donor to the RC. This novel configuration yielded photocurrents orders of magnitude greater than previous reports of electron transfer from the quinone region of RCs bound in this orientation to an electrode.

The concept of hybrid molecules of tacrine and benzyl quinolone carboxylic acid (BQCA) as multifunctional agents for Alzheimer's disease.

Novel tacrine-benzyl quinolone carboxylic acid (tacrine-BQCA) hybrids were designed based on multi-target directed ligands (MTLDs) paradigm, synthesized and evaluated in vitro as inhibitors of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE). Tacrine moiety is represented herein as 7-methoxytacrine, 6-chlorotacrine or unsubstituted tacrine forming three different families of seven members, i.e. 21 compounds in overall. Introducing BQCA, a positive modulator of M1 muscarinic acetylcholine receptors (mAChRs), the action of novel compounds on M1 mAChRs was evaluated via Fluo-4 NW assay on the Chinese hamster ovarian (CHO-M1WT2) cell line. All the novel tacrine-BQCA hybrids were able to block the action of hAChE and hBChE in micromolar to nanomolar range. The hAChE kinetic profile of 5p was found to be mixed-type which is consistent with our docking experiments. Moreover, selected ligands were assessed for their potential hepatotoxicity on HepG2 cell line and presumable permeation through the blood-brain barrier by PAMPA assay. Expected agonistic profile towards M1 mAChRs delivered by BQCA moiety was not confirmed. From all the hybrids, 5o can be highlighted as non-selective cholinesterase inhibitor (hAChE IC50 = 74.5 nM; hBChE IC50 = 83.3 nM) with micromolar antagonistic activity towards M1 mAChR (IC50 = 4.23 µM). A non-selective pattern of cholinesterase inhibition is likely to be valuable during the onset as well as later stages of AD.

Heterologous Production of the Photosynthetic Reaction Center and Light Harvesting 1 Complexes of the Thermophile Thermochromatium tepidum in the Mesophile Rhodobacter sphaeroides and Thermal Stability of a Hybrid Core Complex.

The photosynthetic complexes of the thermophile Thermochromatium tepidum are of considerable interest in biohybrid solar cell applications because of the ability of thermophilic proteins to tolerate elevated temperatures. Synthetic operons encoding reaction center (RC) and light harvesting 1 (LH1) pigment-protein complexes of T. tepidum were expressed in the mesophile Rhodobacter sphaeroides The T. tepidum RC (TRC) was assembled and was found to be functional with the addition of menadione to populate the QA pocket. The production of T. tepidum LH1 (TLH1) was increased by selection of a phototrophy-capable mutant after UV irradiation mutagenesis, which yielded a hybrid RC-TLH1 core complex consisting of the R. sphaeroides RC and T. tepidum TLH1, confirmed by the absorbance peak of TLH1 at 915 nm. Affinity chromatography partial purification and subsequent sucrose gradient analysis of the hybrid RC-TLH1 core complex indicated that this core complex assembled as a monomer. Furthermore, the RC-TLH1 hybrid core complex was more tolerant of a temperature of 70°C than the R. sphaeroides RC-LH1 core complexes in both the dimeric and monomeric forms; after 1 h, the hybrid complex retained 58% of the initial starting value, compared to values of 11% and 53% for the R. sphaeroides RC-LH1 dimer and monomer forms, respectively.IMPORTANCE This work is important because it is a new approach to bioengineering of photosynthesis proteins for potential use in biophotovoltaic solar energy capture. The work establishes a proof of principle for future biohybrid solar cell applications.

Trends in Tramadol: Pharmacology, Metabolism, and Misuse.

Tramadol is a unique analgesic medication, available in variety of formulations, with both monoaminergic reuptake inhibitory and opioid receptor agonist activity increasingly prescribed worldwide as an alternative for high-affinity opioid medication in the treatment of acute and chronic pain. It is a prodrug that is metabolized by cytochrome P450 (CYP) enzymes CYP2D6 and CYP3A4 to its more potent opioid analgesic metabolites, particularly the O-demethylation product M1. The opioid analgesic potency of a given dose of tramadol is influenced by an individual's CYP genetics, with poor metabolizers experiencing little conversion to the active M1 opioid metabolite and individuals with a high metabolic profile, or ultra-metabolizers, experiencing the greatest opioid analgesic effects. The importance of the CYP metabolism has led to the adoption of computer clinical decision support with pharmacogenomics tools guiding tramadol treatment in major medical centers. Tramadol's simultaneous opioid agonist action and serotonin (5-HT) and norepinephrine reuptake inhibitory effects result in a unique side effect profile and important drug interactions that must be considered. Abrupt cessation of tramadol increases the risk for both opioid and serotonin-norepinephrine reuptake inhibitor withdrawal syndromes. This review provides updated important information on the pharmacology, pharmacokinetics, CYP genetic polymorphisms, drug interactions, toxicity, withdrawal, and illicit use of tramadol.

A 7-methoxytacrine-4-pyridinealdoxime hybrid as a novel prophylactic agent with reactivation properties in organophosphate intoxication.

Chemical warfare agents constitute an increasing threat to both military and civilian populations. Therefore, effective prophylactic approaches are urgently needed. Herein, we present a novel hybrid compound which is able not only to keep acetylcholinesterase resistant to organophosphate (OP) inhibitors, but also to serve as an enzyme reactivator in the case of OP intoxication.

Α1-blockers in the management of acute urinary retention secondary to benign prostatic hyperplasia: a systematic review and meta-analysis.

BACKGROUND: α1-Blockers have been widely used in the conservative management of acute urinary retention (AUR). AIMS: To compare the efficacy and safety of α1-blockers in male patients with AUR secondary to benign prostatic hyperplasia (BPH). METHODS: Electronic searches on PubMed/MEDLINE, EMBASE and the Cochrane Library were performed to identify all published randomized controlled trials (RCTs) and controlled clinical trials (CCTs) of α1-blockers for the treatment of AUR. Relevant reviews and reference lists of included studies were explored. RESULTS: Nine studies involving a total of 1051 men were enrolled in this review. Compared to 38.9 % (161/414) in control groups, 56.8 % (362/637) of patients receiving α1-blockers had a successful trial without catheter (TWOC). Meta-analysis demonstrated that α1-blockers have a substantial effect on the successful resumption of micturition after TWOC (RR = 1.45, 95 % CI 1.20-1.75, P = 0.0001). In the subsequent phase, the outcomes across studies indicated that α1-blockers may provide little benefit to maintain the satisfactory voiding without AUR recurrence or BPH surgery in a long-term follow-up. α1-Blockers were generally low and well tolerated in both phases. CONCLUSIONS: In conclusion, α1-blockers provide substantial benefit in increasing a satisfactory micturition within 24 h after TWOC for men with AUR due to BPH, even though the long-term effectiveness remains uncertain.

Use of new strains of Rhodobacter sphaeroides and a modified simple culture medium to increase yield and facilitate purification of the reaction centre.

A new gene expression system was developed in Rhodobacter sphaeroides, replacing a pRK415-based system used previously. The broad host-range IPTG-inducible plasmid pIND4 was used to create the plasmid pIND4-RC1 for expression of the puhA and pufQBALMX genes, encoding the reaction centre (RC) and light-harvesting complex 1 (LH1) proteins. The strain R. sphaeroides ΔRCLH was used to make a knockout of the rshI restriction endonuclease gene, enabling electroporation of DNA into the bacterium; a subsequent knockout of ppsR was made, creating the strain R. sphaeroides RCx lacking this oxygen-sensing repressor of the photosynthesis gene cluster. Using pIND4-RC1, LH1 levels were increased by a factor of about 8 over pRS1 per cell in cultures grown semi-aerobically. In addition, the ppsR knockout allowed for photosynthetic pigment-protein complex synthesis in the presence of high concentrations of molecular oxygen; here, LH1 levels per cell increased by 20 % when grown under high aeration conditions. A new medium (called RLB) is the E. coli medium LB supplemented with MgCl2 and CaCl2, which was found to increase growth rates and final cell culture densities, with an increase of 30 % of LH1 per cell detected in R. sphaeroides RCx(pIND4-RC1) grown in RLB versus LB medium. Furthermore, cell density was about three times greater in RLB compared to semi-aerobic conditions. The combination of all the modifications resulted in an increase of LH1 and RC per mL of culture volume by approximately 35-fold, and a decrease in the length of culture incubation time from about 5 days to ~36 h.

Stigma and perception of psychological distress and depression in Australian-trained medical students: results from an inter-state medical school survey.

Stigmatisation towards depression has previously been reported amongst medical students from a variety of backgrounds. This study explored personal and perceived stigmas associated with depression, and their relationship with demographics, knowledge of depression, levels of personal stress and history of medical illness amongst Australian-trained medical students. A cross-sectional survey was undertaken amongst students enroled June-to-August 2009 across four Australian medical schools. In total, 1010 students completed the survey, a response rate of 29.6%. Approximately 25% of students reported a past history of depression. Higher stress (K-10 scores) was reported by females and those with a past history of depression. On a scale of 0-to-5, the mean (±S.D.) personal and perceived stigma depression scores were 1.83±1.49 and 4.05±1.42 respectively. In multivariate analysis, higher perceived stigma and K-10 scores, a past history of anxiety and Year 3 of medical school indicated higher personal stigma scores. Perceived stigma was positively associated with K-10 scores, personal stigma scores, and a Caucasian background. Our findings suggest a high level of personal and particularly perceived stigma associated with depression amongst medical students, especially those displaying higher levels of stress. Adequate support and screening for psychological stress may de-stigmatise depression and improve mental health amongst future Australian doctors.

The summary on non-reactivation cholinergic properties of oxime reactivators: the interaction with muscarinic and nicotinic receptors.

Organophosphorus inhibitors (OP) of acetylcholinesterase (AChE) represent a group of highly toxic compounds. The treatment of OP intoxication is, however, insufficiently ensured. Currently, two main categories of drugs-anticholinergics and oxime reactivators- are employed as antidotes. Oximes have been reported to act at several levels of the cholinergic transmission, and among the non-reactivation effects, the interaction with cholinergic receptors stands out. This review addresses issues correlated with non-reactivating effects of oxime reactivators with a special focus on the muscarinic and nicotinic receptors, but involvement of other cholinergic structures such as AChE and choline uptake carriers are discussed too. It can be concluded that the oxime reactivators show a variation in their antagonistic effect on the muscarinic and nicotinic receptors, which is likely to be of significance in the treatment of OP poisoning. In vitro data reported oximes to exert higher efficacy on the muscarinic M2 subtype than on the AChE. However, this effect seemed to be subtype specific since the antagonistic M3 effect was lower. Also, and importantly, the antimuscarinic effect was larger than that on nicotinic receptors. Even though atropine showed a much higher muscarinic antagonism, it is supposed that non-reactivation properties of oxime reactivators play a significant role in the treatment of OP poisoning.

Risk factors for malignancy in patients with solitary thyroid nodules and their impact on the management.

BACKGROUND: Presently it is difficult to differentiate malignancy for thyroid nodules by palpation, ultrasonography and fine-needle aspiration cytology (FNAC) at the outpatient department, especially for solitary thyroid nodule (STN). So a great emphasis should be placed on the STN. AIMS: The objective of this study was to investigate the predictive clinicopathological risk factors for malignancy in patients with STN and further to provide an appropriate clinical management. MATERIALS AND METHODS: The records were reviewed from 265 patients with STN who had undergone thyroidectomy in our hospital. All cases were classified as two independent groups in terms of the final pathological results to assess the independent risk factors using a multinomial logistic regression analysis. RESULTS: A multinomial logistic analysis revealed that the male gender, microcalcification and cervical lymphadenopathy were independent risk factors related to malignancy in patients with STN. The incidence of malignancy in patients with 0,1,2,3 risks was 10.71%, 26.6%, 61.43%, and 100%, respectively. CONCLUSIONS: Male gender, microcalcification and lymphadenopathy were independent risk factors for predicting the malignancy in patients with STN. Patients with more than two of those risk factors should be subjected to further examination or thyroidectomy. The findings may provide a simple and reasonable management for the STN.