Monolignol export by diffusion down a polymerization-induced concentration gradient.

Lignin, the second most abundant biopolymer, is a promising renewable energy source and chemical feedstock. A key element of lignin biosynthesis is unknown: how do lignin precursors (monolignols) get from inside the cell out to the cell wall where they are polymerized? Modeling indicates that monolignols can passively diffuse through lipid bilayers, but this has not been tested experimentally. We demonstrate significant monolignol diffusion occurs when laccases, which consume monolignols, are present on one side of the membrane. We hypothesize that lignin polymerization could deplete monomers in the wall, creating a concentration gradient driving monolignol diffusion. We developed a two-photon microscopy approach to visualize lignifying Arabidopsis thaliana root cells. Laccase mutants with reduced ability to form lignin polymer in the wall accumulated monolignols inside cells. In contrast, active transport inhibitors did not decrease lignin in the wall and scant intracellular phenolics were observed. Synthetic liposomes were engineered to encapsulate laccases, and monolignols crossed these pure lipid bilayers to form polymer within. A sink-driven diffusion mechanism explains why it has been difficult to identify genes encoding monolignol transporters and why the export of varied phenylpropanoids occurs without specificity. It also highlights an important role for cell wall oxidative enzymes in monolignol export.

[Assessment of a post-emergency pathway with early urological regulation]. / Analyse d'un modèle de circuit court post-urgence avec une régulation précoce urologique.

INTRODUCTION: Urological emergencies represent 7 % of the outpatients at the emergency department (ED). We assessed the effect of setting up a post-emergency consultation (CPU) after deferred urological medical regulation. METHODS: All patients admitted to the ED in a university center over the period December 2017 to July 2018 and for whom a CPU was scheduled were included. The regulation concerned the date of CPU and supplementary exams. The main outcome was the ability to provide an efficient response according to a predefined grid of specific solutions. RESULTS: One hundred and twenty-eight patients were included. The median age was 57 years (18-97). Efficacy of the CPU was 76 %. This rate was lower in no-show patients or consulting for rare and complex motives (47 %, n=60). The no-show were not reachable on the first call in 51.6 % of cases, with a similar age and motives distribution to the others. Only 6,9 % (n=128) of all consultants (n=1863) had been referred to the CPU by emergency physicians. The decision was a second consultation in 70 % (48), a new exam in 10 % (7), deferred emergency surgery in 12 % (8) and finally 18 % (12) of no follow-up. CONCLUSION: CPU following early regulation by a urologist provides an effective response in 76 % of situations. Assessment of "no-shows" helped to identify groups at risk. LEVEL OF EVIDENCE: III.

[Percutaneous nephrolithotomy for kidney stones in elderly patients: Meta-analysis of results and complications]. / Néphrolithotomie percutanée des calculs rénaux des personnes âgées : méta-analyse des résultats et complications.

INTRODUCTION AND OBJECTIVE: Percutaneous nephrolithotomy (PCNL) is the gold standard treatment for kidney stones regardless of age. Elderly patients (EP)≥65years old, in growing numbers, have more comorbidities than the general population, may alter results of PCNL. The aim of this meta-analysis was to compare efficacy and complications of this procedure between EP and young patients (YP). METHODS: Original studies of prospective and historical cohorts, in English or French, presenting PCNL series published on PubMed until 2015 were identified using the keywords percutaneous nephrolithotomy, elderly patients, kidney stones and staghorn calculi. Our analysis focused on therapeutic efficacy, defined by absence of residual fragment or the presence of residual fragments<4mm at 3 postoperative months, and postoperative complications according to patient age: YP<65 years old and EP≥65 years old. Binary qualitative data were analyzed using odds ratio (OR) and quantitative data by estimating the difference of means. RESULTS: In total 397 studies were identified among which 23 were checked and 8 included in the meta-analysis for methodological quality corresponding to 4995 YP and 820 EP. No efficacy difference (OR=0.96; [IC95 %: 0.80; 1.17]; P=0.71), operating time (+1.15min in EP [IC95 %: -2.83; 5.12]; P=0.57) and average length of stay (+0.29 days in EP [IC95 %: -0.14; 0.72]; P=0.19) has been reported. It was a trend to more urinary infections (OR=2.24; [IC95 %: 0.74-6.80]; P=0.16) and a significantly increase of postoperative blood transfusions in EP (OR=1.41; [IC95 %: 1.00-1.97]; P=0.04). CONCLUSIONS: PCNL for kidney stones n EP is effective with a significantly increase the risk of postoperative blood transfusions compared to YP.

The optimal regimen of bevacizumab for recurrent glioblastoma: does dose matter?

The FDA-approved schedule and dose of bevacizumab (BVZ) for recurrent glioblastoma (rGB) (10 mg/kg q 2 weeks) were adopted from systemic cancer protocols. No dose-defining studies have been performed for glioblastoma. We began using BVZ for the treatment of rGB in 2005 at the dose of 5 mg/kg every 2 weeks combined with irinotecan, and later as single agent. Our previous report of 20 patients treated with BVZ 5 mg/kg every 2 weeks showed similar response rates and overall survival (OS) compared to other BVZ treatment protocols, with less adverse effects. In this study we retrospectively reviewed our 7 year experience with BVZ in 162 rGB patients. Treatment outcomes were analyzed from 87 patients who received BVZ at 5 mg/kg and 75 patients at 10 mg/kg. While median age was similar in both groups, the median KPS was significantly higher in the group treated with 10 mg/kg BVZ (85 versus 60). There was no significant difference in OS or progression free survival (PFS) between the groups treated with BVZ 5 versus 10 mg/kg. Overall survival was significantly improved in the subgroup treated with cytotoxic therapy in addition to BVZ 10 mg/kg. There were more adverse events seen with BVZ 10 mg/kg. There is no significant difference in OS for rGB treated with BVZ 5 mg/kg versus 10 mg/kg when given as monotherapy. The smaller dose was slightly less toxic. Addition of cytotoxic therapy resulted in prolongation of OS in a small subgroup of BVZ 10 mg/kg.

Sex differences in zonulin in affective disorders and associations with current mood symptoms.

INTRODUCTION: The bidirectional connection between the brain and the gut within psychiatric entities has gained increasing scientific attention over the last years. As a regulator of intestinal permeability, zonulin acts as a key player on the interface of this interplay. Like several psychiatric disorders, intestinal permeability was associated with inflammation in previous findings. METHODS: In this study we explored differences in zonulin serum levels in currently depressed (n = 55) versus currently euthymic (n = 37) individuals with an affective disorder. Further, we explored sex differences and possible influences on zonulin and affective symptoms like medication, age, body mass index, and smoking status. RESULTS: Serum zonulin was significantly higher in females than in men independent from affective status (z = -2.412, p = .016). More specifically, females in the euthymic subgroup had higher zonulin levels than euthymic men (z = -2.114, p = .035). There was no difference in zonulin serum levels in individuals taking or not taking a specific psychopharmacotherapy. We found no correlation between zonulin serum levels and depression severity. DISCUSSION: Increased serum zonulin levels as a proxy for increased intestinal permeability in women may indicate a state of elevated susceptibility for depression-inducing stimuli.

Dwarfism of high-monolignol Arabidopsis plants is rescued by ectopic LACCASE overexpression.

Lignin is a key secondary cell wall chemical constituent, and is both a barrier to biomass utilization and a potential source of bioproducts. The Arabidopsis transcription factors MYB58 and MYB63 have been shown to upregulate gene expression of the general phenylpropanoid and monolignol biosynthetic pathways. The overexpression of these genes also results in dwarfism. The vascular integrity, soluble phenolic profiles, cell wall lignin, and transcriptomes associated with these MYB-overexpressing lines were characterized. Plants with high expression of MYB58 and MYB63 had increased ectopic lignin and the xylem vessels were regular and open, suggesting that the stunted growth is not associated with loss of vascular conductivity. MYB58 and MYB63 overexpression lines had characteristic soluble phenolic profiles with large amounts of monolignol glucosides and sinapoyl esters, but decreased flavonoids. Because loss of function lac4 lac17 mutants also accumulate monolignol glucosides, we hypothesized that LACCASE overexpression might decrease monolignol glucoside levels in the MYB-overexpressing plant lines. When laccases related to lignification (LAC4 or LAC17) were co-overexpressed with MYB63 or MYB58, the dwarf phenotype was rescued. Moreover, the overexpression of either LAC4 or LAC17 led to wild-type monolignol glucoside levels, as well as wild-type lignin levels in the rescued plants. Transcriptomes of the rescued double MYB63-OX/LAC17-OX overexpression lines showed elevated, but attenuated, expression of the MYB63 gene itself and the direct transcriptional targets of MYB63. Contrasting the dwarfism from overabundant monolignol production with dwarfism from lignin mutants provides insight into some of the proposed mechanisms of lignin modification-induced dwarfism.

Incidence, aetiology and mortality secondary to hypertensive emergencies in a large-scale referral centre in Israel (1991-2010).

Hypertensive emergency (HE) is a life-threatening condition that requires immediate blood pressure (BP) reduction. Although it has been on the decline, the incidence of HE has recently increased in a few countries. The aim of the present retrospective study was to evaluate the incidence, aetiology and 1-year mortality of HE in a large medical centre over a 20-year period (1991-2010). The electronic medical records of all patient files who were hospitalized in the Chaim Sheba Medical Center in Israel from 1991 to 2010 with a primary diagnosis (at admission or discharge) of Malignant Hypertension, Hypertensive Emergency or Accelerated Hypertension were retrieved and analysed. The study interval was divided into four periods of 5 years each. Among 306 files reviewed, only 142 patients had a true HE. Average age at presentation was 63.3±16.5 years. Men were younger than women (59±16 vs 68±16 years; P<0.001). At presentation, most patients (80.3%) had been diagnosed with essential hypertension previously and were undertreated. Average maximum mean arterial pressure (MAP) was higher in men (169±22 mm Hg) than in women (161±17 mm Hg; P=0.026). The rate of HE decreased over the course of the study, from 12.7/100 000 admissions during 1991-1995 to 6.2/100 000 admissions (2006-2010). Similarly, 1-year mortality decreased from 16.7 to 3.6%. The rate of HE has decreased and the prognosis has improved over the last two decades. Appropriate BP control of patients with essential hypertension may further decrease the risk of HE.

Cholesteatoma. A clinical and morphological analysis.

A total of 33 consecutively operated aural cholesteatomas were analysed with regard to preoperative findings and correlated with the morphology of the cholesteatoma tissue. Patients were found in all age groups, 9/33 of the patients were operated at an age below 15 years. A persistent ear discharge had occurred in all patients but in 9 cases the patient history was of less than one year. Impaired hearing was found in 29/33. A demineralization of ossicles was observed at X-ray also in cases in which the ossicular chain appeared normal at operation. In only 5/33 cases was there a retraction of the tympanic membrane without a perforation. The morphological features were the same in both very rapidly and very slowly growing cholesteatomas.

Hearing in patients operated unilaterally for otosclerosis. Self-assessment of hearing and audiometric results.

The objective of this study was to examine the outcome of unilateral stapes surgery in one patient group with bilateral hearing loss and one group with unilateral hearing loss. The patients' own estimations of improvement in hearing ability and the occurrence of other ear-related symptoms were examined retrospectively and in a follow-up study. Ninety-five of 123 patients operated for otosclerosis in only one ear between 1987 and 1992 responded to a follow-up examination. Observed audiometric findings and changes thereof, along with the patients' own estimations of their hearing handicap pre- and postoperatively, and the occurrence of other ear-related symptoms were studied. Despite good surgical results (closure of air-bone gap within 20 dB in 94%), 33% of the patients had severe hearing disabilities postoperatively, and many of these patients needed further amplification with a hearing aid. Mild dizziness occurred in 33% of the patients postoperatively and did not decrease over time. Discomfort in the operated ear due to strong sounds was reported in 20%. Change in sound quality occurred in 80% of the operated ears, but tended to disappear over time. From the results of this study it may be concluded that surgery in one ear only, leaving the other ear with poor hearing, is not an optimal hearing rehabilitation of patients with otosclerosis. It is important endevour to achieve bilateral hearing in order to give the patient good social hearing. Postoperative dizziness and unpleasant hearing quality do occur frequently, and the patients need to be informed about these problems preoperatively.

Symptoms, findings and treatment in patients with dehiscence of the superior semicircular canal.

Recently Minor and co-workers described patients with sound- and pressure-induced vertigo due to dehiscence of the superior semicircular canal. Identifying patients with this 'new' vestibular entity is important, not only because the symptoms are sometimes very incapacitating, but also because they can be treated. We present symptoms and findings in eight such patients, all of whom reported pressure-induced vertigo that increased during periods of upper respiratory infections. Pulse-synchronous tinnitus and gaze instability during head movements were also common complaints. All patients lateralized Weber's test to the symptomatic ear. In some of the patients the audiogram also revealed a small conductive hearing loss. However, the stapedius reflexes were always normal. A vertical/torsional eye movement related to the superior semicircular canal was seen in most of the patients in response to pressure changes and/or sound stimulation. One patient also had superior canal-related positioning nystagmus. Testing vestibular evoked myogenic potentials revealed in all patients a vestibular hypersensitivity to sounds. In the coronal high-resolution 1-mm section CT scans the dehiscence was visible on 1 to 4 sections. Moreover, the skull base was rather thin in this area and cortical bone separating the middle ear and the antrum from the middle cranial fossa was absent in many of the patients. Two of the patients have undergone plugging of the superior semicircular canal using a transmastoid approach and both patients were relieved of the pressure-induced symptoms.

Stimulus presentation level and speech perception through a single-channel cochlear implant.

This study evaluated the effects of stimulus presentation level on 12 adult 3M/House single-channel cochlear implant users' speech perception performance. Dynamic ranges and loudness growth functions were measured for meaningful speech, and performance-intensity functions were plotted for VCV and CVC nonsense stimuli to determine the presentation level(s) that produced maximum speech perception performance for each subject. Considerable variability was found in the subjects' dynamic ranges. Generally, loudness growth functions were steep for subjects having restricted dynamic ranges and more gradual for those having wide dynamic ranges. No single optimal presentation level was determined; instead, a range of levels produced maximum performance for each subject. Mean levels producing peak scores in equivalent dB SPL were 80 for VCVs and 72 for CVCs. Presentation levels producing optimal performance varied with type of speech stimulus.

Performance of 3M/house cochlear implant users on tests of speech perception.

This report documents both closed- and open-set speech recognition performance for 18 adult experienced users of the 3M/House single-channel cochlear implant. The stimuli included tape-recorded, standard word and sentence recognition tests, an environmental-sound test, nonsense syllables, and sentences presented in auditory (implant-only), visual, and auditory-visual modes. All subjects were tested individually in a single session using their own cochlear implants, set to typical comfort use settings for running speech. Subjects' oral responses to the stimuli were transcribed by the experimenters and scored for percent correct. The results revealed considerable individual differences among the subjects and their performance on different tests. All subjects scored better than chance on the closed-set tests. Although they performed considerably poorer on the open-set tests, approximately half of these subjects demonstrated at least some open-set word recognition, a finding not previously reported in the literature for this device. All subjects performed better on the auditory-visual sentences than on either the auditory or visual conditions alone. These results contribute to the database on speech perception by cochlear implant users and show that open-set word recognition performance was somewhat better for these subjects using this implant than would have been predicted from the literature.

A clinical comparison of the results of two different methods of closing tympanic membrane perforations.

A series of myringoplasties is presented and those cases that did not heal perfect are discussed. In order to evaluate whether some changes in the technique could further improve the results, another series incorporating these changes was operated after and the results are presented. Differences in healing and post-operative hearing between the two groups of patients are evaluated.

Healing and hearing in uncomplicated myringoplasty.

In closing an uncomplicated central drum defect the technique known as an 'underlay' is widely used. This method has certain advantages and yields good results as far as both healing and hearing are concerned. In an attempt further to improve results the authors give an account of a series of myringoplasties and specifically discuss the unsuccessful cases. By a slight alteration in the operative technique used in the series presented, the authors believe that some failures can be avoided.

Hearing function in a hyperbaric environment.

Navy divers' hearing function was assessed as part of three saturation deep dives to 1,000 feet of sea water (fsw) to determine explanations for threshold shifts observed under hyperbaric conditions. Across the three deep dives, different aspects of the ear were evaluated, including air- and bone-conduction pure-tone thresholds, real ear probe microphone measurements, auditory evoked potentials, and central auditory processing assessments. Attempts to measure middle ear function and cochlear function (through otoacoustic emissions) were unsuccessful. Baseline measurements were obtained at 0 fsw in air before and after the saturation deep dives. Results showed that some aspects of hearing function remained unchanged with increases in depth. In general, audiometric thresholds at depth were similar to those measured on the surface at 500, 1,000, 2,000, 3,000, and 4,000 Hz. However, hearing sensitivity actually improved at depth at 6,000 and 8,000 Hz. The use of a specially designed sound booth for a pressurized heliox environment yielded significantly lower ambient noise levels and improved the accuracy of threshold measurement. Auditory evoked potential measurements and central auditory processing function were relatively unaffected by changes in depth. Significant changes at depth were seen in ear canal resonance which shifted up in frequency; this finding was attributed to the effect of helium on the hearing mechanism. Because objective measurement of middle ear and inner ear function were not methodologically possible, questions still remain regarding the interpretation of middle and inner ear function at depth. Nonetheless, our overall findings suggest that most aspects of hearing functioning are similar under high atmospheric pressures and in heliox as they are on the surface, with the exception of shifts in ear canal resonance and improvements in audiometric thresholds at high frequencies.

Use of speech production repair strategies to improve diver communication.

The purpose of this investigation was to determine if speech intelligibility improved when divers made specific modifications to their speaking patterns while in a hyperbaric helium-oxygen (heliox) environment. Divers were trained to produce a variety of sentences using speech with three types of alterations: (1) slowed rate, (2) increased loudness, and (3) a combination of slightly slowed rate, a minimal increase in loudness, increased pause time, and greater mouth opening (composite strategy). Both diver and non-diver listeners judged these sentences for intelligibility. In addition, acoustic analysis of the cues for the identification of voicing, place, and manner of articulation was conducted to determine if such cues might become more audible in the speech signal when repair strategies were used. Both perceptual and acoustic results showed the composite method to be the best for natural-sounding, intelligible speech. It had the effect of slowing rate and increasing loudness just enough to increase intelligibility without causing distortion. It was concluded that teaching divers to produce speech using this method would be a worthwhile investment for improving speech intelligibility.

Counseling in audiology, or learning to listen: pre- and post-measures from an audiology counseling course.

Because of a "technology explosion," audiologists have more options than ever in providing for their patients' hearing needs. However, relatively few individuals with hearing loss seek out amplification, and those who do frequently report dissatisfaction with the quality of their interactions with audiologists. Most audiologists did not have coursework in counseling in their graduate programs, which may account for patient complaints. As part of a course development evaluation of an audiology counseling course, a preliminary study was conducted to examine two student learning objectives: to learn how to differentiate between content messages and affective messages and to learn how to respond to each type of message appropriately. Pre- and postcourse data collected from two cohorts of audiology graduate students indicated that (a) before taking the course, students were likely to provide informational responses to personal adjustment comments (a type of "communication mismatch"), and (b) at the end of the class, they were much more likely to match or mirror affective statements with affective responses.

Direct puncture of large arteriovenous malformations in head and neck for embolisation and subsequent reconstructive surgery.

Five patients with large arteriovenous malformations (AVM) of the head and neck, which were too large or inconveniently placed for operation alone, were treated by embolisation after direct puncture; two of them were subsequently operated upon. They all recovered without complications. Embolisation of the nidus and subsequent operation is a good alternative for the treatment of large AVM. Ligating the supplying arteries is not a treatment. If the arterial routes to the nidus have previously been closed by ligatures selective catheterisation is impossible, though direct puncture of the nidus is a possibility. The nidus of the AVM can then be obliterated by embolisation either as a treatment, or as a preoperative procedure.