NLRP1-associated autoinflammatory disease with epithelial dyskeratosis.

Several gain-of-function variants in NLRP1 cause a distinctive autoinflammatory disease reported under different names featuring mainly skin and mucosal involvement and variable systemic signs. Here, we report a new case of NLRP1-associated autoinflammatory disease in a 6-year-old Peruvian girl, who presented with confluent hyperkeratotic plaques that drained purulent material with subsequent scarring. A c.3641C > G (p. Pro1214Arg) variant that has been previously been reported was found in NLRP1 and was not present in either parent. The term NLRP1-associated autoinflammatory disease with epithelial dyskeratosis (NADED) is proposed to encompass all reported cases, which have received different nomenclature so far.

Detailed measurements of oesophageal pressure during mechanical ventilation with an advanced high-resolution manometry catheter.

BACKGROUND: Oesophageal pressure (PES) is used for calculation of lung and chest wall mechanics and transpulmonary pressure during mechanical ventilation. Measurements performed with a balloon catheter are suggested as a basis for setting the ventilator; however, measurements are affected by several factors. High-resolution manometry (HRM) simultaneously measures pressures at every centimetre in the whole oesophagus and thereby provides extended information about oesophageal pressure. The aim of the present study was to evaluate the factors affecting oesophageal pressure using HRM. METHODS: Oesophageal pressure was measured using a high-resolution manometry catheter in 20 mechanically ventilated patients (15 in the ICU and 5 in the OR). Different PEEP levels and different sizes of tidal volume were applied while pressures were measured continuously. In 10 patients, oesophageal pressure was also measured using a conventional balloon catheter for comparison. A retrospective analysis of oesophageal pressure measured with HRM in supine and sitting positions in 17 awake spontaneously breathing patients is also included. RESULTS: HRM showed large variations in end-expiratory PES (PESEE) and tidal changes in PES (ΔPES) along the oesophagus. Mean intra-individual difference between the minimum and maximum end-expiratory oesophageal pressure (PESEE at baseline PEEP) and tidal variations in oesophageal pressure (ΔPES at tidal volume 6 ml/kg) recorded by HRM in the different sections of the oesophagus was 23.7 (7.9) cmH2O and 7.6 (3.9) cmH2O respectively. Oesophageal pressures were affected by tidal volume, level of PEEP, part of the oesophagus included and patient positioning. HRM identified simultaneous increases and decreases in PES within a majority of individual patients. Compared to sitting position, supine position increased PESEE (mean difference 12.3 cmH2O), pressure variation within individual patients and cardiac artefacts. The pressure measured with a balloon catheter did not correspond to the average pressure measured with HRM within the same part of the oesophagus. CONCLUSIONS: The intra-individual variability in PESEE and ΔPES is substantial, and as a result, the balloon on the conventional catheter is affected by many different pressures along its length. Oesophageal pressures are not only affected by lung and chest wall mechanics but are a complex product of many factors, which is not obvious during conventional measurements. For correct calculations of transpulmonary pressure, factors influencing oesophageal pressures need to be known. HRM, which is available at many hospitals, can be used to increase the knowledge concerning these factors. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02901158.

Effect of positive end-expiratory pressure on gastric insufflation during induction of anaesthesia when using pressure-controlled ventilation via a face mask: A randomised controlled trial.

BACKGROUND: Face mask ventilation (FMV) during induction of anaesthesia is associated with risk of gastric insufflation that may lead to gastric regurgitation and pulmonary aspiration. A continuous positive airway pressure (CPAP) has been shown to reduce gastric regurgitation. We therefore hypothesised that CPAP followed by FMV with positive end-expiratory pressure (PEEP) during induction of anaesthesia would reduce the risk of gastric insufflation. OBJECTIVE: The primary aim was to compare the incidence of gastric insufflation during FMV with a fixed PEEP level or zero PEEP (ZEEP) after anaesthesia induction. A secondary aim was to investigate the effects of FMV with or without PEEP on upper oesophageal sphincter (UES), oesophageal body and lower oesophageal sphincter (LES) pressures. DESIGN: A randomised controlled trial. SETTING: Single centre, Department of Anaesthesia and Intensive Care, Örebro University Hospital, Sweden. PARTICIPANTS: Thirty healthy volunteers. INTERVENTIONS: Pre-oxygenation without or with CPAP 10 cmH2O, followed by pressure-controlled FMV with either ZEEP or PEEP 10 cmH2O after anaesthesia induction. MAIN OUTCOME MEASURES: A combined impedance/manometry catheter was used to detect the presence of gas and to measure oesophageal pressures. The primary outcome measure was the cumulative incidence of gastric insufflation, defined as a sudden anterograde increase in impedance of more than 1 kΩ over the LES. Secondary outcome measures were UES, oesophageal body and LES pressures. RESULTS: The cumulative incidence of gastric insufflation related to peak inspiratory pressure (PIP), was significantly higher in the PEEP group compared with the ZEEP group (log-rank test P < 0.01). When PIP reached 30 cmH2O, 13 out of 15 in the PEEP group compared with five out of 15 had shown gastric insufflation. There was a significant reduction of oesophageal sphincter pressures within groups comparing pre-oxygenation to after anaesthesia induction, but there were no significant differences in oesophageal sphincter pressures related to the level of PEEP. CONCLUSION: Contrary to the primary hypothesis, with increasing PIP the tested PEEP level did not protect against but facilitated gastric insufflation during FMV. This result suggests that PEEP should be used with caution after anaesthesia induction during FMV, whereas CPAP during pre-oxygenation seems to be safe. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02238691.

Does the ß-receptor antagonist esmolol have analgesic effects?: A randomised placebo-controlled cross-over study on healthy volunteers undergoing the cold pressor test.

BACKGROUND: Esmolol may attenuate the sympathetic response to pain and reduce postoperative opioid consumption. It is not clear whether esmolol has an analgesic effect per se. OBJECTIVES: The aim of this study was to evaluate the analgesic effect of esmolol in the absence of anaesthetics and opioids. We tested the hypothesis that esmolol would reduce the maximum pain intensity perceived during the cold pressor test (CPT) by 2 points on a 0 to 10 numeric pain rating scale (NRS) compared to placebo. DESIGN: Randomised, placebo-controlled cross-over study. SETTING: Postoperative recovery area, Örebro University Hospital. Study period, November 2013 to February 2014. PARTICIPANTS: Fourteen healthy volunteers. Exclusion criteria included ongoing medication, pregnancy and breastfeeding and participation in other medical trials. INTERVENTIONS: At separate study sessions, participants received interventions: esmolol (0.7 mg kg bolus over 1 min followed by infusion at 10 µg kg min); 0.9% normal saline bolus then remifentanil infusion at 0.2 µg kg min and 0.9% normal saline bolus and infusion according to a random sequence. All infusions were administered over 30 min. MAIN OUTCOME MEASURES: Perceived maximum pain intensity score, pain tolerance and haemodynamic changes during CPT, and occurrence of side-effects to interventions compared to placebo, respectively. RESULTS: Esmolol did not reduce perceived pain intensity or pain tolerance during the CPT. The NRS-max score was similar for esmolol, 8.5 (±1.4) and placebo, 8.4 (±1.3). The mean difference was 0.1 [95% confidence interval (-1.2 to 1.4)], P value equal to 0.83. Remifentanil significantly reduced NRS-max scores, 5.4 (±2.1) compared to placebo, [mean difference -3.1 (95% confidence interval (-4.4 to -1.8)), P < 0.001]. Side-effects were seen with remifentanil but not with esmolol. CONCLUSION: No direct analgesic effect of esmolol could be demonstrated in the present study. The postoperative opioid-sparing effect demonstrated in previous studies, could therefore be secondary to other factors such as avoidance of opioid-induced hyperalgesia, synergy with coadministered opioids or altered pharmacokinetics of those drugs. TRIAL REGISTRATION: European clinical trials database, https://eudract.ema.europa.eu/, EudraCT no. 2011-005780-24.

Effects of Esmolol on the Esophagogastric Junction: A Double-Blind, Randomized, Crossover Study on 14 Healthy Volunteers.

BACKGROUND: Passive regurgitation may occur throughout the perioperative period, increasing the risk for pulmonary aspiration and postoperative pulmonary complications. Hypnotics and opioids, especially remifentanil, that are used during anesthesia have been shown to decrease the pressure in the esophagogastric junction (EGJ), that otherwise acts as a barrier against passive regurgitation of gastric contents. Esmolol, usually used to counteract tachycardia and hypertension, has been shown to possess properties useful during general anesthesia. Like remifentanil, the ß-1-adrenoreceptor antagonist may be used to attenuate the stress reaction to tracheal intubation and to modify perioperative anesthetic requirements. It may also reduce the need for opioids in the postoperative period. Its action on the EGJ is however unknown.The aim of this trial was to compare the effects of esmolol and remifentanil on EGJ pressures in healthy volunteers, when administrated as single drugs. METHODS: Measurements of EGJ pressures were made in 14 healthy volunteers using high-resolution solid-state manometry. Interventions were administered in a randomized sequence and consisted of esmolol that was given IV as a bolus dose of 1 mg/kg followed by an infusion of 10 µg·kg·minute over 15 minutes, and remifentanil with target-controlled infusion of 4 ng/mL over 15 minutes. Interventions were separated by a 20-minute washout period. Analyses of EGJ pressures were performed at baseline, and during drug administration at 2 (T2) and 15 minutes (T15). The primary outcome was the inspiratory EGJ augmentation, while the inspiratory and expiratory EGJ pressures were secondary outcomes. RESULTS: There was no effect on inspiratory EGJ augmentation when comparing remifentanil and esmolol (mean difference -4.0 mm Hg [-9.7 to 1.7]; P= .15). In contrast, remifentanil significantly decreased both inspiratory and expiratory pressures compared to esmolol (-12.2 [-18.6 to -5.7]; P= .003 and -8.0 [-13.3 to -2.8]; P= .006). CONCLUSIONS: Esmolol, compared with remifentanil, does not affect EGJ function. This may be an advantage regarding passive regurgitation and esmolol may thus have a role to play in anesthesia where maintenance of EGJ barrier function is of outmost importance.

Individual and sex distinctiveness in bark calls of domestic chinchillas elicited in a distress context.

Animals obtain information about their social environment by means of communication signals, which provide relevant subtle cues for individual recognition. An important requisite for this process is the existence of larger between- than within-emitter signal variation. Acoustic signals are complex traits susceptible of variation in their spectral and temporal components, implying that signal distinctiveness can result from differences in single or various acoustic components. In this study, domestic chinchillas were induced to vocalize in a distress context to describe the acoustic characteristics of the bark calls, and to determine features that denote the potential value of this vocalization for individual and/or sexual recognition. The results demonstrate that the variation in spectral and temporal components of the bark calls of chinchillas elicited under a distress context is larger between than within individuals, suggesting the potential of these signals for distinctiveness between individual signalers, although the potential of this call type for sex distinctiveness is quite limited. These results combined with previous studies on auditory capabilities of chinchillas contribute to position this rodent as a valuable model species for studying auditory-vocal interactions.

Personality and misinformation.

Misinformation poses a significant concern, promoting false beliefs and eroding trust in media. People differ in their susceptibility to believe and to share misinformation. In this article, we reviewed recent research on relationships between personality traits and belief in and sharing of misinformation. Findings show that more extroverted and less conscientious and agreeable people tend to be more susceptible to believing in and sharing misinformation. Additionally, the Dark Triad personality traits of narcissism, psychopathy, and Machiavellianism tend to be positively associated with sharing of misinformation, and narcissism and psychopathy are associated with greater belief in misinformation. Understanding these individual differences can inform interventions to reduce the effects of misinformation.

Malignant syphilis as the presenting complaint of advanced HIV.

Malignant syphilis is an infrequent secondary manifestation in patients with human immunodeficiency virus (HIV), with polymorphous and disseminated skin lesions being related to severe immunosuppression. Lesions have intense inflammatory circinate, ulcer-crusted and nodular skin lesions of diffuse distribution throughout the body, that can be confused with vasculitis or cutaneous lymphomas. We report a patient recently diagnosed with HIV infection in the acquired immunodeficiency syndrome stage with malignant syphilis as the debut of HIV.

Graphene nanocomposite for biomedical applications: fabrication, antimicrobial and cytotoxic investigations.

Materials possessing excellent bacterial toxicity, while presenting low cytotoxicity to human cells, are strong candidates for biomaterials applications. In this study, we present the fabrication of a nanocomposite containing poly(N-vinylcarbazole) (PVK) and graphene (G) in solutions and thin films. Highly dispersed PVK-G (97-3 w/w%) solutions in various organic and aqueous solvents were prepared by solution mixing and sonication methods. The thermal properties and morphology of the new composite were analyzed using thermal gravimetry analysis (TGA) and atomic force microscopy (AFM), respectively. PVK-G films were immobilized onto indium tin oxide (ITO) substrates via electrodeposition. AFM was used to characterize the resulting topography of the nanocomposite thin films, while cyclic voltammetry and UV-vis were used to monitor their successful electrodeposition. The antimicrobial properties of the electrodeposited PVK-G films and solution-based PVK-G were investigated against Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis). Microbial growth after exposure to the nanocomposite, metabolic assay and live-dead assay of the bacterial solutions exposed to PVK-G presented fewer viable and active bacteria than those exposed to pure PVK or pure graphene solutions. The PVK-G film inhibited about 80% of biofilm surface coverage whereas the PVK- and G-modified surfaces allowed biofilm formation over almost the whole coated surface (i.e. > 80%). The biocompatibility of the prepared PVK-G solutions on NIH 3T3 cells was evaluated using the MTS cell proliferation assay. A 24 h exposure of the PVK-G nanocomposite to the NIH 3T3 cells presented ~80% cell survival.

Effects of propofol on oesophageal sphincters: a study on young and elderly volunteers using high-resolution solid-state manometry.

BACKGROUND AND OBJECTIVE: The oesophageal sphincters play an important role in protecting the airway. During manometric studies, administration of an anxiolytic agent is often required to make insertion of the catheter acceptable for the patient. The anxiolytic should not affect the results of the measurements. This study evaluates the effects of two different doses of propofol on the pressures in the oesophageal sphincters. The effect of increased abdominal pressure was also studied. METHODS: Twenty healthy volunteers, 10 young (mean age 25 years) and 10 elderly (mean age 71 years), were recruited. The effects of a low dose of propofol [0.3 mg kg(-1) intravenously (i.v.)] and a high dose of propofol (young group 0.9 mg kg(-1) i.v. and elderly group 0.6 mg kg(-1) i.v.) were studied with and without external abdominal pressure. RESULTS: There were no statistically significant changes in lower oesophageal sphincter (LOS) pressure after the low dose of propofol. After the high dose, there was an increase in LOS pressure, which was statistically significant in the young group (P < 0.05). The upper oesophageal sphincter (UOS) pressure decreased after both doses of propofol (P < 0.01 for the higher dose and P < 0.05 for the lower dose). CONCLUSION: A low dose of propofol (0.3 mg kg(-1) i.v.) leaves the LOS unaffected in young and elderly volunteers and can be used safely as an anxiolytic agent during studies of the LOS without influencing the results. However, the UOS is more sensitive to the effects of propofol and we do not recommend the use of propofol as an anxiolytic agent during manometric studies of the UOS.

High-resolution solid-state manometry of the upper and lower esophageal sphincters during anesthesia induction: a comparison between obese and non-obese patients.

BACKGROUND: The prevalence of obesity has increased dramatically in recent decades. The gastrointestinal changes associated with obesity have clinical significance for the anesthesiologist in the perioperative period. The lower esophageal sphincter and the upper esophageal sphincter play a central role in preventing regurgitation and aspiration. The effects of increased intra-abdominal pressure during anesthesia on the lower esophageal sphincter and the upper esophageal sphincter in obese patients are unknown. In the present study we evaluated, with high-resolution solid-state manometry, the upper esophageal sphincter, lower esophageal sphincter, and barrier pressure (BrP) (lower esophageal pressure--gastric pressure) in obese patients during anesthesia induction and compared them with pressures in non-obese patients. METHODS: We studied 28 patients, ages 18 to 72 years, 14 with a body mass index > or = 35 kg/m(2), who were undergoing laparoscopic gastric bypass, and 14 with a body mass index < or = 30 kg/m(2), who were undergoing laparoscopic cholecystectomy, using high-resolution solid-state manometry. RESULTS: Upper esophageal sphincter pressure decreased during anesthesia induction in both groups. Lower esophageal sphincter pressure decreased in both groups during anesthesia induction, and it was significantly lower in obese patients than in non-obese patients. The BrP decreased in both groups and was significantly lower in the obese group than in the non-obese group. The BrP remained positive at all times in both groups. CONCLUSION: Lower esophageal sphincter and BrPs decreased in both obese and non-obese patients during anesthesia induction, but were significantly lower in obese patients. Although the BrP was significantly lower, it remained positive in all patients.

Corneal endothelial cell loss associated to phacoemulsification and ophthalmologist experience: prospective analysis of individual secondary data. / Pérdida celular endotelial corneal asociada a facoemulsificación y experiencia del oftalmólogo: análisis prospectivo de datos secundarios individuales.

INTRODUCTION: Phacoeresis is the procedure through which the lens is surgically removed to treat cataracts. A corneal endothelial loss is a recognized sequel. Although several factors associated with this harm have been described, the surgeon’s prior experience has been scarcely evaluated. OBJECTIVES: To assess the association between the surgeon’s experience and other variables associated with a corneal endothelial cell loss in the context of phacoeresis. METHODS: Clinical records of 198 patients undergoing cataract operations were prospectively reviewed. The experience of the surgeon and other variables were recorded, including cumulative dissipated energy, viscoelastic type, the use of trypan blue, amount of fluidics, ultrasound time, combined phacoemulsification energy, and pre- and postoperative corneal endothelial cell counts. RESULTS: No differences were observed in the postoperative corneal endothelial cell count between surgeons with more or less than five years of experience. Nevertheless, ophthalmologists with more than five years’ experience used less trypan blue, but more cumulative dissipated energy in each procedure, while less experienced ophthalmologists used less fluidics. CONCLUSIONS: Although there were differences in the surgical management regarding the surgeons’ experience in factors known to influence corneal endothelial cell loss, no differences in endothelial cell loss were observed as an outcome.

INTRODUCCIÓN: La facoéresis es el procedimiento en que se extrae quirúrgicamente el cristalino para tratar las cataratas. La pérdida endotelial corneal es una complicación reconocida. Si bien se han descrito diversos factores asociados a este daño, la experiencia del cirujano ha sido poco explorada. OBJETIVOS: Evaluar la asociación entre la experiencia del cirujano y otras variables asociadas a la pérdida celular endotelial en el contexto de la facoéresis. MÉTODOS: Se analizaron registros clínicos de 198 cirugías de cataratas, evaluando el efecto de la experiencia del cirujano y otras variables asociadas: energía disipada acumulada, tipo de viscoelástico empleado, uso de azul tripán, cantidad de fluídica, tiempo de ultrasonido, energía de facoemulsificación combinada y recuento celular endotelial pre y postoperatorio. RESULTADOS: No se observaron diferencias en el conteo postoperatorio de células endoteliales. Los oftalmólogos con más de cinco años de experiencia presentaron menor uso de azul tripán pero mayor cantidad de energía disipada acumulada en cada procedimiento, mientras que los oftalmólogos con menor experiencia utilizaron mayor cantidad de fluídica. CONCLUSIONES: Aunque hubo diferencias en el manejo de algunos factores influyentes sobre la pérdida endotelial cornal según la experiencia de los oftalmólogos, no se hallaron diferencias en relación a dicha pérdida como resultado final.

Time-to-intubation in obese patients. A randomized study comparing direct laryngoscopy and videolaryngoscopy in experienced anesthetists.

BACKGROUND: Airway management may be difficult in obese patients. Moreover, during prolonged intubation, oxygen desaturation develops rapidly. Videolaryngoscopy improves the view of the larynx, and the Storz® C-MAC™ has been shown to be superior to other videolaryngoscopes in terms of intubation time in obese patients. However, no effort has been made to compare the Storz® C-MAC™ with direct laryngoscopy. The aim of the study was to evaluate if the use of Storz® C-MAC™ may reduce intubation time when compared to direct laryngoscopy (classic Macintosh® blade). METHODS: Eighty patients with Body Mass Index >35 kg/m2 were randomized to orotracheal intubation using either Macintosh® laryngoscope, or the Storz® C-MAC™ with the standard Macintosh blade. Patients had no previous history of a difficult airway. Time-to-intubation (TTI) was defined as the time from the moment anesthetist took the laryngoscope until end-tidal carbon dioxide was detected. RESULTS: No significant difference in TTI could be demonstrated between the two devices tested (mean difference -1.7 s (95% CI:-6.9 to 3.5 s). All patients in the videolaryngoscopy group were successfully intubated with the allocated device, whereas five patients in the direct laryngoscopy group required an alternative device for successful intubation. No significant difference regarding the subjective difficulty of intubation and postoperative sore throat between groups was demonstrated. CONCLUSIONS: In obese patients the airway may be secured equally fast using direct laryngoscopy (Macintosh®) and with videolaryngoscopy using the Stortz® C-MAC™. The risk for failed intubation, however, appears to be greater with direct laryngoscopy, especially in male obese patients.

Incontinencia pigmentaria / Incontinentia pigmenti

RESUMEN La incontinencia pigmentaria es una genodermatosis de rara presentación, que es considerada una alteración hereditaria, ligada al cromosoma X, con carácter dominante. Se presenta con mayor frecuencia en mujeres, y el compromiso principal se observa en tejidos derivados del ectodermo; es decir, puede evidenciarse como anormalidades en piel, dientes, pelos, ojos y sistema nervioso. Se presenta un caso de incontinencia pigmentaria con manifestaciones cutáneas en un recién nacido varón. El caso se confirmó a través de dos biopsias evaluadas en el servicio de anatomía patológica del Hospital Cayetano Heredia. Debido al espectro amplio de presentación clínica de incontinencia pigmentaria, se recomienda considerar a esta entidad en el diagnóstico diferencial cuando nos encontramos frente a lesiones cutáneas, predominantemente vesiculares y que siguen una distribución siguiendo las líneas de Blaschko. La incontinencia pigmentaria es una enfermedad infrecuente en nuestro país, y su diagnóstico requiere de una adecuada correlación clínico patológica, y del conocimiento de las distintas fases de la enfermedad. El diagnóstico y reconocimiento oportuno y temprano de la entidad permitirá prevenir complicaciones asociadas a nivel sistémico.

ABSTRACT Incontinentia Pigmenti is a rare genodermatosis, which is considered a hereditary alteration, linked to the X chromosome, with a dominant character. It occurs more frequently in women, and the main involvement is observed in tissues derived from the ectoderm, that is, it can be seen as abnormalities in the skin, teeth, hair, eyes and nervous system. We report a case of incontinentia pigmenti with cutaneous manifestations in a male newborn is presented. The case was confirmed through two biopsies evaluated in the pathological anatomy service of the Cayetano Heredia Hospital. Due to the broad spectrum of clinical presentation of incontinence pigmenti, it is recommended to consider this entity in the differential diagnosis when we are faced with predominantly vesicular skin lesions that follow a distribution along Blaschko lines. Incontinentia pigmenti is a rare disease in our country, and its diagnosis requires an adequate clinicopathological correlation, and knowledge of the different phases of the disease. The timely and early diagnosis and recognition of the entity will prevent associated complications at the systemic level.

The aging digestive tract: what should anesthesiologists know about it?

At present, elderly individuals represent approximately 18.5% of the European population and account for about 23% of surgical procedures performed. This patient population is at a higher risk for perioperative complications and adverse postoperative outcome. This narrative review highlights our current knowledge about physiological changes in the aging gut and the implications for anesthesiologists. The reduced response to stimuli in the pharynx, and reduction of the cough reflex that occurs in many older individuals, probably explains the increased incidence of aspiration pneumonia that occurs in the elderly. These changes also increase the risk for aspiration during anesthesia. Aging affects the clearance of fluids and solids in the esophagus, associated with a higher incidence of gastro-esophageal reflux disease. Healthy aging appears to be associated with modest slowing of gastric emptying, but this does not demand prolonged preoperative fasting. The physiological changes associated with polypharmacy also make elderly patients a risk group for pulmonary aspiration during anesthesia. Further research is needed to determine the effects of commonly used anesthetic agents on the pharyngo-gastrointestinal tract in elderly patients.

The Corticofugal Effects of Auditory Cortex Microstimulation on Auditory Nerve and Superior Olivary Complex Responses Are Mediated via Alpha-9 Nicotinic Receptor Subunit.

BACKGROUND AND OBJECTIVE: The auditory efferent system is a complex network of descending pathways, which mainly originate in the primary auditory cortex and are directed to several auditory subcortical nuclei. These descending pathways are connected to olivocochlear neurons, which in turn make synapses with auditory nerve neurons and outer hair cells (OHC) of the cochlea. The olivocochlear function can be studied using contralateral acoustic stimulation, which suppresses auditory nerve and cochlear responses. In the present work, we tested the proposal that the corticofugal effects that modulate the strength of the olivocochlear reflex on auditory nerve responses are produced through cholinergic synapses between medial olivocochlear (MOC) neurons and OHCs via alpha-9/10 nicotinic receptors. METHODS: We used wild type (WT) and alpha-9 nicotinic receptor knock-out (KO) mice, which lack cholinergic transmission between MOC neurons and OHC, to record auditory cortex evoked potentials and to evaluate the consequences of auditory cortex electrical microstimulation in the effects produced by contralateral acoustic stimulation on auditory brainstem responses (ABR). RESULTS: Auditory cortex evoked potentials at 15 kHz were similar in WT and KO mice. We found that auditory cortex microstimulation produces an enhancement of contralateral noise suppression of ABR waves I and III in WT mice but not in KO mice. On the other hand, corticofugal modulations of wave V amplitudes were significant in both genotypes. CONCLUSION: These findings show that the corticofugal modulation of contralateral acoustic suppressions of auditory nerve (ABR wave I) and superior olivary complex (ABR wave III) responses are mediated through MOC synapses.

Comparison of stereoscopic digital imaging and slide film photography in the identification of macular degeneration.

BACKGROUND: This study compared the sensitivity and specificity of stereoscopic digital photography of the retina through a dilated pupil with a 45 degrees nonmydriatic camera and Joint Photographic Experts Group (JPEG) compression of the images with the sensitivity and specificity of 35-mm slide film photography in the identification of age-related macular degeneration (AMD). METHODS: Consecutive patients with a diagnosis of AMD were enrolled. Stereoscopic retinal images of the disc, macula and temporal macula were captured with a digital 45 degrees nonmydriatic camera (then compressed into JPEG format) and with a standard fundus camera and slide film. A single retinal specialist graded both image formats in masked fashion, at least 1 month apart, using a modified Age-Related Eye Disease Study (AREDS) severity scale. The digital images were displayed on a monitor and viewed with the use of liquid crystal display shutter glasses and stereo imaging software. The film images were mounted on a light box and graded with the use of a stereoviewer. Primary outcome measures included the presence or absence of AMD pathological features. Positive and negative predictive values (PPVs and NPVs), sensitivity, specificity and weighted kappaw statistics were calculated. RESULTS: We photographed 203 eyes (of 103 patients) with both digital and slide film cameras. Correlation of the 2 image formats was substantial in identifying AREDS level 3a or greater (kappaw=0.64, standard error=0.08, PPV=0.95, NPV=0.66, sensitivity=0.93, specificity=0.74) and excellent in identifying level 4b or greater (kappaw=0.83, standard error=0.05, PPV=0.81, NPV=0.98, sensitivity=0.94, specificity=0.94). INTERPRETATION: High-resolution stereoscopic, mydriatic, 45 degrees digital images captured with a nonmydriatic camera and JPEG compressed correlate well with stereoscopic slide film photographs in the identification of moderate to advanced AMD (AREDS level 3a or greater).

Developments in alternative treatments for organophosphate poisoning.

Organophosphosphates (OPs) are highly effective acetylcholinesterase (AChE) inhibitors that are used worldwide as cheap, multi-purpose insecticides. OPs are also used as chemical weapons forming the active core of G-series and V-series chemical agents including tabun, sarin, soman, cyclosarin, VX, and their chemical analogs. Human exposure to any of these compounds leads to neurotoxic accumulation of the neurotransmitter acetylcholine, resulting in abnormal nerve function and multiple secondary health complications. Suicide from deliberate exposure to OPs is particularly prevalent in developing countries across the world and constitutes a major global health crisis. The prevalence and accessible nature of OP compounds within modern agricultural spheres and concern over their potential use in biochemical weapon attacks have incentivized both government agencies and medical researchers to enact stricter regulatory policies over their usage and to begin developing more proactive medical treatments in cases of OP poisoning. This review will discuss the research undertaken in recent years that has investigated new supplementary drug options for OP treatment and support therapy, including progress in the development of enzymatic prophylaxis.

Detection and location of OP-degrading activity: A model to integrate education and research.

The Environmental Sampling Research Module (ESRM) is an investigative/discovery module that provides undergraduate research experiences for students as part of an interdisciplinary research-based biotechnology curriculum at the University of Houston campus. As part of the ESRM, students collect soil samples from various locations to test for the presence of organophosphorous (OP) degrading bacteria. At the end of this research project students submit a research paper on their field and laboratory activities and discuss their experimental data and observations. Students also record the date, location of collection, and the results of testing the sample for the degradation of two pesticides, methyl parathion or paraoxon, in an electronic laboratory notebook (ELN). Each collection site is recorded on a Google Maps module and the data from student research activities is made available to other undergraduate students. This data is then used to generate a microorganism database of pesticide degrading activity and promote reading, critical thinking, and analytical skills as part of the curriculum. Our sampling of agricultural sites and wastewater within and around the city of Houston has identified seven distinct genera of OP degrading organisms, including Pseudomonas, Stenotrophomonas, Exiguobacterium, Delftia, Agrobacterium, Aeromonas, and Rhizobium. Collected strains exhibit phosphotriesterase-like enzymatic activity with isolates of Pseudomonas putida and Stenotrophomonas maltophilia capable of degrading both the phosphotriester paraoxon and the phosphorothioate methyl parathion. Using this collection of OP-degrading microorganisms, undergraduate students have evaluated their potential for enhancing the removal of harmful organophosphates and their toxic metabolites from contaminated agricultural soil and adjacent bodies of water. This analytical data can potentially be utilized for environmental and industrial applications in bioremediation and ecology providing an innovative method for integrating education and research. In addition, the versatility of the ESRM itself provides for easy and rapid adaptation into varying environmental science courses with significant potential for the discovery and isolation of new and unique organisms to be used as part of ongoing research in the laboratory.