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.

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.

[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.

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.

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.

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.

[Methods for core temperature measurements].

The measurement of core temperature is important for many clinical situations including heat illnesses, hypothermia, infections, sepsis, shock, hemorrhage, and exposure to chemical and biological agents. Currently, oral and rectal temperatures are clinically utilized for such measurements. However, oral measurements are not always possible and accurate whereas rectal measurements are not convenient in the field, are labor intensive, use fragile glassware containing mercury--an environmental contaminant, require sterilization and are not suited for mass casualties. A simple, non-invasive, non-breakable, inexpensive device to measure core temperature, which is not labor intensive, would have great use in the field and in hospitals, as well as provide an important advance in instrumentation for experimental physiology. The purpose of this work is to evaluate the different methods for core temperature measurement. Since the middle of the 18th century, the mercury thermometer has been almost the only instrument for measuring core temperature. Today, more sophisticated methods and instruments are gaining popularity. In addition, new promising converted techniques, which are about to enter the market and increase the available variety of instruments, might improve the situation as far as reliability and convenience of use are concerned. Despite the importance and usage of this variable, the progress in this field has been slower than would have been expected.

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.

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.

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.

Speech intelligibility assessment in a helium environment. II. The speech intelligibility index.

The Speech Intelligibility Index (SII) was measured for Navy divers participating in two saturation deep dives and for a group of nondivers to test different communication systems and their components. These SIIs were validated using the Speech Perception in Noise (SPIN) test and the Griffiths version of the Modified Rhyme Test (GMRT). Our goal was to determine if either of these assessments was sensitive enough to provide an objective measure of speech intelligibility when speech was processed through different helmets and helium speech unscramblers (HSUs). Results indicated that SII values and percent intelligibility decreased incrementally as background noise level increased. SIIs were very reliable across the different groups of subjects indicating that the SII was a strong measurement for predicting speech intelligibility to compare linear system components such as helmets. The SII was not useful in measuring intelligibility through nonlinear devices such as HSUs. The speech intelligibility scores on the GMRT and SPIN tests were useful when the system component being compared had a large measurable difference, such as in helmet type. However, when the differences were more subtle, such as differences in HSUs, neither the SPIN nor the GMRT appeared sensitive enough to make such distinctions. These results have theoretical as well as practical value for measuring the quality and intelligibility of helium speech enhancement systems.

Otorrhagia from the "aberrant internal carotid" artery in the middle ear. Surgical and endovascular aspects.

SUMMARY: Agenesis of the cervical portion of the internal carotid artery (ICA) may result in blood supply to the ipsilateral cerebral hemisphere being provided by an enlarged inferior tympanic branch of the ascending pharyngeal artery. This enlarged vessel, passing through Jacobson's canal and anastomosing with the likewise enlarged caroticotympanic branch of the ICA in front of the promontorium, may simulate a middle ear mass. We present five patients with this unusual anatomical variant, three of which underwent biopsy of what was believed to be a middle ear tumour. One patient experienced rupture of an arterial aneurysm in the middle ear successfully treated with endovascular application of detachable platinum coils. It is mandatory for ENT-surgeons and radiologists who perform head-and-neck examinations to recognize this anatomical variant, not mistaking it for a tumour, since biopsy of a large artery supplying the brain may have disastrous consequences. In patients with otorrhagia, an arterial aneurysm must be considered as a possible source of bleeding, in some cases amenable for treatment with an endovascular technique. The diagnosis of "aberrant internal carotid artery"" is usually made with CT of the temporal bone or MR of the skull base. Cerebral angiography is in most cases not necessary, unless an endovascular procedure is planned.

Congenital malformation of the inner ear and recurrent meningitis. A case report.

Congenital deformities of the inner ear can be associated with meningitis and varying degrees of hearing loss or deafness. Recurrent periods of meningitis, sometimes lethal, are due to communication between the middle ear cavity and the subarachnoid space. Different types of congenital dysplasia have been classified earlier and we report a 3-year-old girl with unilateral deafness, episodes of meningitis and a malformation of the inner ear and the footplate of the stapes.