Occupational health screening during Gurkha Central Selection: a retrospective cohort study.

OBJECTIVE: The selection process to the British Army's Brigade of Gurkhas is rigorous, demanding and competitive. The ethos of recruitment to the Gurkhas is grounded in an overarching tenant: that selection is free, fair and transparent. The aim of this study was to retrospectively review reasons for potential recruits (PRs) to be deemed medically unsuitable or deferred suitability on medical grounds for selection to the Brigade of Gurkhas. METHODS: A retrospective review was conducted by extracted data from published post-exercise reports for the past four years to ascertain numbers of PRs deemed medically fit, medically unsuitable or deferred suitability on medical grounds. The International Classification of Disease version 11 (ICD-11) codes were retrospectively assigned to code medical reasons for non-progression. Rates of medical non-progression were compared by year. RESULTS: A total of 3154 PRs were analysed between 2018 and 2021. There was no significant difference between PRs deemed medically fit and those deemed medically suitable or deferred on medical grounds over the study period (p=0.351). There was a significant difference in the ratio of PRs deferred on medical grounds and those deemed medically unsuitable over the study period (p<0.05). CONCLUSION: Selection to the Gurkhas is extremely competitive. These data demonstrate that, overall, reasons for medical deferral or unsuitability have remained constant despite the impact of a global pandemic. These data reinforce the central tenant of Gurkha selection; that it continues to be free, fair, and transparent.

EELS: Autonomous snake-like robot with task and motion planning capabilities for ice world exploration.

Ice worlds are at the forefront of astrobiological interest because of the evidence of subsurface oceans. Enceladus in particular is unique among the icy moons because there are known vent systems that are likely connected to a subsurface ocean, through which the ocean water is ejected to space. An existing study has shown that sending small robots into the vents and directly sampling the ocean water is likely possible. To enable such a mission, NASA's Jet Propulsion Laboratory is developing a snake-like robot called Exobiology Extant Life Surveyor (EELS) that can navigate Enceladus' extreme surface and descend an erupting vent to capture unaltered liquid samples and potentially reach the ocean. However, navigating to and through Enceladus' environment is challenging: Because of the limitations of existing orbital reconnaissance, there is substantial uncertainty with respect to its geometry and the physical properties of the surface/vents; communication is limited, which requires highly autonomous robots to execute the mission with limited human supervision. Here, we provide an overview of the EELS project and its development effort to create a risk-aware autonomous robot to navigate these extreme ice terrains/environments. We describe the robot's architecture and the technical challenges to navigate and sense the icy environment safely and effectively. We focus on the challenges related to surface mobility, task and motion planning under uncertainty, and risk quantification. We provide initial results on mobility and risk-aware task and motion planning from field tests and simulated scenarios.

COVID-19 infection and maternal morbidity in critical care units in Scotland: a national cohort study.

BACKGROUND: Previous research has shown that, in comparison with non-pregnant women of reproductive age, pregnant women with COVID-19 are more likely to be admitted to critical care, receive invasive ventilation, and die. At present there are limited data in relation to outcomes and healthcare utilisation following hospital discharge of pregnant and recently pregnant women admitted to critical care. METHODS: A national cohort study of pregnant and recently pregnant women who were admitted to critical care in Scotland with confirmed or suspected COVID-19. We examined hospital outcomes as well as hospital re-admission rates. RESULTS: Between March 2020 and March 2022, 75 pregnant or recently pregnant women with laboratory-confirmed COVID-19 were admitted to 24 Intensive Care Units across Scotland. Almost two thirds (n=49, 65%) were from the most deprived socio-economic areas. Complete 90-day acute hospital re-admission data were available for 74 (99%) patients. Nine (12%) women required an emergency non-obstetric hospital re-admission within 90 days. Less than 5% of the cohort had received any form of vaccination. CONCLUSIONS: This national cohort study has demonstrated that pregnant or recently pregnant women admitted to critical care with COVID-19 were more likely to reside in areas of socio-economic deprivation, and fewer than 5% of the cohort had received any form of vaccination. More targeted public health campaigning across the socio-economic gradient is urgently required.

Patient engagement in the Continuing Professional Development programs within the department of radiation oncology at the University of Toronto (UTDRO): A qualitative study.

INTRODUCTION: There is little research regarding patient engagement (PE) in Continuing Professional Development (CPD) programs in radiation oncology. This study aims to understand the barriers and enablers to PE in the design and implementation process of CPD programs, and advance PE in these programs moving forward. METHODS: This qualitative study involved 17 semi-structured interviews, with 5 cancer patients and 12 educators, conducted from June 2019 to April 2020. Interview data identified common themes, such as: the current state of PE in CPD programming, and key barriers and recommendations on how to engage patients in meaningful and practical ways. RESULTS: Six themes were identified related to PE: the concept of PE, ethical considerations, barriers, key considerations in planning resources, and the anticipated impact of PE on curriculum planning. CONCLUSION: Both patients and educators emphasized that creating and sustaining meaningful educator-patient relationships and giving patients an active and effective role in CPD planning would improve curriculum content. The University of Toronto Department of Radiation Oncology (UTDRO) should consider building this initiative into its strategic CPD priorities and ensure the appropriate infrastructure is in place.

The changing epidemiology of radial head replacement over a 22-year period in Scotland.

BACKGROUND: Radial head replacement is used to confer joint stability in the management of acute unstable elbow fractures and dislocations associated with instability. We determined the annual incidence of radial head replacement over a 22-year period in a defined population. MATERIALS AND METHODS: Hospital episode statistics were collected prospectively at a national level. This database was retrospectively examined to determine the annual incidence of radial head replacement over the study period in adults over 16 years of age. RESULTS: A total of 615 radial head replacements were performed over the 22 years studied. The overall incidence was 0.65/100,000/year (95% confidence interval, CI, 0.50-0.71). The average adult population during the period was 4,270,593. There was a steady and statistically significant increase in the incidence of radial head replacement over the study period (r 2 = 0.816; p < 0.0001). This incidence was significantly greater in women than men (odds ratio 1.46, 95% CI 1.25-1.72; p < 0.001). The peak incidence in men was 0.87/100,000 population/year in the fifth decade of life while in women the peak incidence was in the seventh decade of life (1.38/100,000 population/year). CONCLUSION: The incidence of radial head replacement has increased steadily over 22 years. We hypothesise that this represents an evolving understanding of the role of radial head replacement in acute trauma in the context of emerging literature during the study period.

Predictors of death and new disability after critical illness: a multicentre prospective cohort study.

PURPOSE: This study aimed to determine the prevalence and predictors of death or new disability following critical illness. METHODS: Prospective, multicentre cohort study conducted in six metropolitan intensive care units (ICU). Participants were adults admitted to the ICU who received more than 24 h of mechanical ventilation. The primary outcome was death or new disability at 6 months, with new disability defined by a 10% increase in the WHODAS 2.0. RESULTS: Of 628 patients with the primary outcome available (median age of 62 [49-71] years, 379 [61.0%] had a medical admission and 370 (58.9%) died or developed new disability by 6 months. Independent predictors of death or new disability included age [OR 1.02 (1.01-1.03), P = 0.001], higher severity of illness (APACHE III) [OR 1.02 (1.01-1.03), P < 0.001] and admission diagnosis. Compared to patients with a surgical admission diagnosis, patients with a cardiac arrest [OR (95% CI) 4.06 (1.89-8.68), P < 0.001], sepsis [OR (95% CI) 2.43 (1.32-4.47), P = 0.004], or trauma [OR (95% CI) 6.24 (3.07-12.71), P < 0.001] diagnosis had higher odds of death or new disability, while patients with a lung transplant [OR (95% CI) 0.21 (0.07-0.58), P = 0.003] diagnosis had lower odds. A model including these three variables had good calibration (Brier score 0.20) and acceptable discriminative power with an area under the receiver operating characteristic curve of 0.76 (95% CI 0.72-0.80). CONCLUSION: Less than half of all patients mechanically ventilated for more than 24 h were alive and free of new disability at 6 months after admission to ICU. A model including age, illness severity and admission diagnosis has acceptable discriminative ability to predict death or new disability at 6 months.

Ataxia por celiaquía / Celiac disease and cerebellar ataxia

INTRODUCCIÓN: En la enfermedad celíaca las manifestaciones extraintestinales, con ausencia de las intestinales clásicas, son cada vez más frecuentes. La ataxia por gluten es una manifestación frecuente en adultos con celiaquía, pero en pediatría se considera excepcional. CASO CLÍNICO: Presentamos un caso de un niño de 11 años con ataxia progresiva de difícil diagnóstico, con marcadores serológicos de celiaquía prácticamente normales y con diagnóstico por biopsia intestinal, y con respuesta positiva a inmunoglobulinas intravenosas y dieta libre de gluten. CONCLUSIÓN: Puede resultar recomendable en pacientes con ataxia cerebelosa realizar un tipado de HLA junto a valoración de serología de celiaquía, y en caso de sospecha realizar panendoscopia digestiva oral

INTRODUCTION: Extraintestinal manifestations in the celiac disease, in absence of the classic intestinal ones, are increasingly frequent. Gluten ataxia is a frequent manifestation in adults with celiac disease. It is, nonetheless, considered exceptional in pediatrics. CASE REPORT: We present a case of an 11-year-old boy with progressive ataxia difficult to diagnose, with practically normal serologic markers of celiac disease, diagnosed by intestinal biopsy and with a positive response to intravenous immunoglobulins and a gluten-free diet. CONCLUSION: It may be advisable in patients with cerebellar ataxia to perform an HLA typing along with an assessment of celiac disease serology, and in case of suspicion of performing oral digestive panendoscopy

Hematuria recidivante como síntoma guía del síndrome del desfiladero aortomesentérico / Recurrent hematuria as a guiding symptom of aortomesenteric gorge síndrome

INTRODUCCIÓN: Este síndrome define la compresión de la vena renal izquierda entre la aorta y la arteria mesentérica superior, provocando una presión elevada de dicha vena renal con posible desarrollo de venas colaterales. Clínicamente, aparece hematuria intermitente, proteinuria con o sin dolor abdominal o en hemiabdomen izquierdo. CASOS CLÍNICOS: Presentamos 15 niños de entre 7 y 13 años, la mayoría con examen físico normal y clínica de dolor abdominal o del flanco izquierdo con presión arterial normal (46,6%); hallazgos urinarios: hematuria no glomerular (20%) y proteinuria de rango no nefrótico (20%), con microalbúmina inferior a 300 mg en orina de 24 horas. Un paciente (6,7%) presentó proteinuria asociada a glucosuria e hipertensión. Las mediciones de ultrasonografía Doppler del diámetro anteroposterior (AP) y las velocidades máximas de la vena renal izquierda son diagnósticas: dilatación y enlentecimiento del flujo proximal a la pinza aortomesentérica, disminución del calibre con flujo acelerado a nivel distal y ángulo de la pinza menor de 30º. En dos casos precisó angio-TAC, mostrando la vena renal izquierda comprimida entre la aorta y la arteria mesentérica superior. La angiografía por RM ofrece una excelente definición anatómica. El tratamiento es conservador. Puede ser necesario tratamiento con inhibidores de la enzima convertidora de la angiotensina, intervenciones quirúrgicas o procedimientos extravasculares. CONCLUSIÓN: Sospechar SHVR ante la presencia de hematuria, proteinuria, dolor abdominal recurrente, diagnóstico que requiere alto índice de sospecha. Precisa ecografía. En casos seleccionados, angio-TAC, RM o flebografía, siendo esta última el gold standard para el diagnóstico, que no suele precisarse

INTRODUCTION: This syndrome defines the compression of the left renal vein between the aorta and the superior mesenteric artery, causing an elevated pressure of said renal vein with possible development of collateral veins. Clinically, intermittent hematuria, proteinuria appears with or without abdominal pain or in the left abdomen. CLINICAL CASES: We present 15 children between 7 and 13 years old. Most with normal physical and clinical examination of abdominal or left flank pain with normal blood pressure (46.6%); urinary findings: non-glomerular hematuria (20%) and non-nephrotic range proteinuria (20%), with microalbumin less than 300 mg in 24-hour urine. One patient (6.7%) presented proteinuria associated with glucosuria and hypertension. Doppler ultrasound measurements of the anteroposterior diameter (AP) and the maximum velocities of the left renal vein are diagnostic: dilatation and slowing of the flow proximal to the aortomesenteric clamp, decrease in caliber with accelerated flow at the distal level and angle of the clamp less than 30º. In two cases, angio-TAC was required, showing the compressed left renal vein between the aorta and the superior mesenteric artery. MR angiography offers excellent anatomical definition. The treatment is conservative. Treatment with angiotensin-converting enzyme inhibitors, surgery, or extravascular procedures may be necessary. CONCLUSION: Suspect RVS, in the presence of hematuria, proteinuria, recurrent abdominal pain, a diagnosis that requires a high index of suspicion. Requires ultrasound. In selected cases, CT angiography, MRI or phlebography, the latter being the gold standard for diagnosis, which is not usually required

Presentación de un síndrome hiponatrémico-hipertensivo como síndrome de poliuria-polidipsia / Hyponatremic-hypertensive syndrome presenting as a polyuria-polydipsia syndrome

El síndrome hiponatrémico-hipertensivo es infrecuente en niños. Se caracteriza por la presencia de hipertensión de origen renovascular y trastornos hidroelectrolíticos, asociado a hiponatremia, que conduce a una depleción de sodio y agua, lo que se define como natriuresis por presión. La mayoría de los casos publicados en los pacientes pediátricos presentan síntomas neurológicos agudos acompañados de vómitos, retraso del crecimiento y pérdida de peso. Sólo D’Angelo et al. describieron 2 casos similares con SHH y síndrome poliuria-polidipsia, pero ambos asociados a un tumor de Wilms. Presentamos el caso de un niño de 2 años de edad con síndrome hiponatrémico-hipertensivo, encontrado durante un estudio de poliuria-polidipsia. Aunque los valores de presión arterial eran extremadamente altos, el paciente no presentaba clínica neurológica. Los niveles de actividad de renina plasmática y aldosterona estaban elevados. La arteriografía reveló la existencia de una estenosis de una arteria renal accesoria del riñón derecho. Tras un tratamiento antihipertensivo intensivo, el paciente pudo someterse a cirugía, alcanzando posteriormente valores normales de presión arterial y desapareciendo la poliuria y la polidipsia. Este caso supone una presentación del síndrome hiponatrémico-hipertensivo no descrita hasta ahora, y confirma que la hipertensión renovascular puede manifestarse sólo como un síndrome de poliuria-polidipsia a pesar de presentar valores extremadamente elevados de presión arterial (AU)

Although reported in adults, hyponatremic-hypertensive syndrome is an infrequent disorder in children. It is characterized by hypertension of renovascular origin and electrolyte disorder mainly profound hyponatremia leading to sodium and water depletion (pressure natriuresis). Most of cases published in pediatric patients present acute neurological symptoms accompanied with others than vomiting, failure to thrive, polyuria-polydipsia and weight loss. Only D’Angelo et al. described two similar cases with hyponatremic-hypertensive syndrome and polyuria-polydipsia syndrome in two children associated both with Wilms tumor. We present the case of a two years-old infant with a hyponatremic-hypertensive syndrome found within the study of polyuria and polidypsia. Although blood pressure values extremely high, the patient didn´t present neurological features. The peripheral rennin activity and aldosterone levels were both elevated. The angiographic studies were performed and o stenosis of an accessory renal artery on right kidney. After intensive antihypertensive treatment the patient underwent surgical correction and became normotensive with only low dose enalapril, serum electrolyte values, thirst and urine volume became normal. Our case confirms that renovascular hypertension, can onset only as a poliuria-polydipsia syndrome despite extremely elevated values of blood pressure. We finally want must emphasize the role of arterial pressure control in children with hypostenuric conditions (AU)

Mars Science Laboratory relative humidity observations: Initial results.

The Mars Science Laboratory (MSL) made a successful landing at Gale crater early August 2012. MSL has an environmental instrument package called the Rover Environmental Monitoring Station (REMS) as a part of its scientific payload. REMS comprises instrumentation for the observation of atmospheric pressure, temperature of the air, ground temperature, wind speed and direction, relative humidity (REMS-H), and UV measurements. We concentrate on describing the REMS-H measurement performance and initial observations during the first 100 MSL sols as well as constraining the REMS-H results by comparing them with earlier observations and modeling results. The REMS-H device is based on polymeric capacitive humidity sensors developed by Vaisala Inc., and it makes use of transducer electronics section placed in the vicinity of the three humidity sensor heads. The humidity device is mounted on the REMS boom providing ventilation with the ambient atmosphere through a filter protecting the device from airborne dust. The final relative humidity results appear to be convincing and are aligned with earlier indirect observations of the total atmospheric precipitable water content. The water mixing ratio in the atmospheric surface layer appears to vary between 30 and 75 ppm. When assuming uniform mixing, the precipitable water content of the atmosphere is ranging from a few to six precipitable micrometers. KEY POINTS: Atmospheric water mixing ratio at Gale crater varies from 30 to 140 ppmMSL relative humidity observation provides good dataHighest detected relative humidity reading during first MSL 100 sols is RH75.

Clinical practice recommendations for depression.

OBJECTIVE: To provide clinically relevant evidence-based recommendations for the management of depression in adults that are informative, easy to assimilate and facilitate clinical decision making. METHOD: A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. The recommendations then underwent consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. RESULTS: The clinical practice recommendations for depression (Depression CPR) summarize evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. CONCLUSION: These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of individual factors in the management of depression. Further, the novel style and practical approach should promote uptake and implementation.

Clinical practice recommendations for bipolar disorder.

OBJECTIVE: To provide clinically relevant evidence-based recommendations for the management of bipolar disorder in adults that are informative, easy to assimilate and facilitate clinical decision-making. METHOD: A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. These preliminary recommendations underwent extensive consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. RESULTS: The clinical practice recommendations for bipolar disorder (bipolar CPR) summarise evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. CONCLUSION: These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of individual factors in the management of bipolar disorder. Further, the novel style and practical approach should promote their uptake and implementation.

Genetic mapping of genes conferring permethrin resistance in the malaria vector, Anopheles gambiae.

Resistance to permethrin in an East African population of the major malaria vector, Anopheles gambiae is multifactorial. A mutated sodium channel allele and enhanced insecticide metabolism contribute to the resistance phenotype. We used microsatellite markers to scan the genome for quantitative trait loci (QTL) associated with permethrin resistance. Two major and one minor QTL were identified. The first QTL, rtp1, colocalizes with the sodium channel gene on chromosome 2L thus further supporting the importance of mutations in this gene in conferring permethrin resistance. The second two loci are located on the third chromosome and one of these, rtp2, flanks a large cluster of cytochrome P450 genes. Further detailed mapping of these regions will help elucidate the molecular mechanisms of metabolic resistance to insecticides.

Prevalence of caseous lymphadenitis and usage of caseous lymphadenitis vaccines in sheep flocks.

OBJECTIVE: To estimate the prevalence of caseous lymphadenitis (CLA), determine the current usage of vaccines against CLA and to measure the effectiveness of these vaccines on sheep farms. DESIGN AND POPULATION: A survey was undertaken on 223 sheep flocks in New South Wales, Victoria and Western Australia. METHOD: The prevalence of CLA was measured by conventional inspection techniques at abattoirs in lines of sheep that could be traced back to a farm. Managers of the flocks were sent a questionnaire about their vaccine practices, management practices and knowledge of CLA. RESULTS: The average prevalence of CLA in adult sheep in these flocks was 26% and varied from 20% in Western Australia to 29% in New South Wales. About 43% of sheep producers used CLA vaccines; only 12% used them as recommended. Awareness of CLA was highest in Western Australia. More producers would use CLA vaccine if they knew the prevalence of CLA in their flock and producers obtained most information about CLA from vaccine resellers. CONCLUSIONS: Only 10 to 15% of producers are currently achieving effective CLA control through the use of recommended CLA vaccination programs. In Western Australian flocks more than 25% of effectively vaccinated ewes will be sent to abattoirs in the 2 to 3 years after this study. However, large decreases in the prevalence of CLA can be achieved by about 70% of producers by either making adjustments to their vaccination programs or buying a vaccine with a CLA component. Two or three key facts on effective CLA vaccination could be made available at the point of sale of vaccines and from abattoirs that reported the prevalence of CLA to farmers.

Effect of mulesing and shearing on the prevalence of effect of mulesing and shearing on the prevalence of Erysipelothrix rhusiopathiae arthritis in lambs.

OBJECTIVE: To examine the effects of management practices and environment on the prevalence of arthritis in lambs. DESIGN AND POPULATION: A case-control study was conducted on groups of lambs from 122 Western Australian sheep flocks. METHOD: Arthritis was diagnosed by visual assessment of lambs at abattoirs by qualified meat inspectors. The prevalence was estimated from data collected from producers on culling practices for arthritis. Data on management practices and environmental variables were collected by personal interview. Stepwise logistic regression was used to measure the effects of the most important factors on the prevalence of arthritis. RESULTS: Mulesing and shearing lambs increased the odds of high prevalence of arthritis by 7 (95% CI 1.9 - 25.6) and 4.3 (95% CI 0.9 - 19.6) times, respectively compared to unmarked and unshorn lambs. Lambs slaughtered between December and June had 3.7 (95% CI 0.8 - 16.6) times greater odds of having a high prevalence of arthritis than lambs slaughtered in the remainder of the year. CONCLUSIONS: This study indicates that, to decrease the risk of high prevalence of arthritis, lambs raised for meat production should not be mulesed or shorn. Recommended improvements to hygiene at mulesing such as the use of portable yards had little effect on the prevalence of arthritis.

Effect of the interval between shearing and dipping on the spread of Corynebacterium pseudotuberculosis infection in sheep.

OBJECTIVE: To determine whether the spread of Corynebacterium pseudotuberculosis infection to sheep in dips could be controlled by increasing the time between shearing and dipping. DESIGN: A controlled treatment trial where only the time between shearing and dipping was varied. ANIMALS AND PROCEDURE: One hundred and ninety-five sheep were found to be negative for C. pseudotuberculosis exposure by assay of CLA toxin antibody, were divided into four treatment groups. Each was shorn at either 0, 2, 4 or 8 weeks before dipping in a solution containing C. pseudotuberculosis. Blood samples were taken 6 weeks after dipping and sheep were slaughtered 12 weeks after dipping. A fifth smaller group of 14 sheep shorn 26 weeks before dipping, was also exposed to C. pseudotuberculosis and was slaughtered with the other sheep. RESULTS: The occurrence of caseous lymphadenitis abscesses did not differ between groups or with sheep shorn 26 weeks before dipping. The proportion of sheep that seroconverted to the C. pseudotuberculosis toxin and cell wall ELISA was larger in sheep dipped immediately after shearing than in sheep in the other groups. CONCLUSIONS: Delaying dipping until 8 weeks after shearing did not decrease the C. pseudotuberculosis infection rate due to dipping. Sheep dipped immediately after shearing developed higher concentrations of antibody to C. pseudotuberculosis than sheep when dipping occurred between 2 and 8 weeks and later after shearing.

Developmental depression of glutamate neurotransmission by chronic low-level activation of NMDA receptors.

Slabs of slow-release plastic (Elvax) containing NMDA or solvent were implanted over the rat colliculus beginning on postnatal day 8 (P8). Whole-cell patch clamping in the superficial superior collicular layers (sSCs) from P10 to P21 demonstrated a severe decrease in spontaneous EPSC frequency after chronic NMDA treatment. The decrease was not attributable to an increase in GABA(A) receptor-mediated inhibition and was present only when NMDA receptor (NMDAR) current was blocked by Mg(2+). Analysis of miniature EPSCs indicated that many active sites on NMDA-treated neurons lacked functional AMPA and kainate receptor (AMPA/KAR) currents, and AMPA/KAR:NMDAR current ratios of evoked EPSCs were also significantly reduced. In addition, the normal downregulation of NMDAR decay time in sSC neurons at P11 was absent after NMDA treatment. Nevertheless, neither AMPA nor NMDA receptor subunit expression was altered by NMDA treatment, and experiments with the NMDAR antagonist ifenprodil suggested that incorporation of NR2A-containing NMDARs at the sSC synapses was unperturbed. Thus, disrupting but not blocking NMDARs suppresses the development of AMPA/KAR currents. The absence of the P11 NMDAR current downregulation is likely a secondary effect resulting from the reduction of AMPA/KAR function. Chronic agonist application reduces but does not eliminate NMDAR conductances. Therefore these data support an active role for NMDAR currents in synaptic development. Prolonged NMDA treatment in vivo, which couples reduced postsynaptic Ca(2+) responses with normally developing afferent activity, produces a long-lasting synaptic depression and stalls glutamatergic synaptogenesis, suggesting that the correlation between robust NMDAR activation and afferent activity is an essential component during normal development.

[Ventricular arrhythmias induced by appropriate antibradycardia pacing in patients with implantable defibrillators]. / Inducción de arritmias ventriculares por estimulación antibradicardia apropiada en pacientes portadores de desfibrilador automático.

INTRODUCTION AND OBJECTIVES: The induction of ventricular arrhythmias by appropriate antibradycardia ventricular pacing in patients with implantable cardioverter defibrillators has been reported in only a few cases. The aim of this study was to assess the incidence, characteristics and management of these episodes. METHODS: The follow-up records of 180 patients with implantable cardioverter defibrillators with intracardiac electrogram storage were reviewed. Pacing induced episodes were defined as those occurring immediately after an appropriate paced stimulus in a patient with sporadic paced beats. We assessed the number and type of episodes, mode of onset, therapy administered and the efficacy of different prevention measures. RESULTS: Pacing induced episodes were found in 9 patients (5%). Seven received device administered therapy which was effective in all cases. One to 95 episodes were observed per patient, of which 138 were monomorphic ventricular tachycardias and 20 polymorphic ventricular tachycardia/ventricular fibrillation episodes. All were induced by a paced ventricular beat after a post-extrasystolic pause or after long RR intervals during atrial fibrillation. Pacing induced arrhythmias were prevented by changing the pacing rate or hysteresis in 3 out of 6 patients and by decreasing the stimulus energy in 3 out of 3. Antibradycardia pacing function was disabled in 4 patients. CONCLUSIONS: Ventricular arrhythmias induced by appropriate antibradycardia ventricular pacing are relatively common in patients with implantable cardioverter defibrillators. Effective prevention can be achieved in most cases by changing the pacing rate or the pacing stimulus energy, however in selected cases the antibradycardia function may be disabled.

Chronic NMDA receptor blockade from birth increases the sprouting capacity of ipsilateral retinocollicular axons without disrupting their early segregation.

We have investigated the role of the NMDA glutamate receptor (NMDAR) in the genesis and regulation of structural plasticity during synaptogenesis in the visual layers of the rat superior colliculus (sSC). In this neuropil, three projections compete for synaptic space during development. By fluorescently labeling the projections of both eyes and imaging them with confocal microscopy, we can quantify the sprouting of the ipsilateral retinal projection that follows removal of a portion of the contralateral retinal and/or corticocollicular projection. Using these techniques we have studied the effects of NMDAR blockade under different levels of competition. NMDARs were chronically blocked from birth [postnatal day 0 (P0)] by suspending the competitive antagonist 2-amino-5-phosphonopentanoic acid in the slow release plastic Elvax, a slab of which was implanted over the sSC. Such treatment alone does not impair the normal segregation of the retinal projections. However, if sprouting of the ipsilateral projection is initiated with a small contralateral retinal lesion at P6, this sprouting can be further increased by blocking NMDARs from birth. Sprouting of the ipsilateral retinal projection is also induced by retinal lesions made at P10/P11, but NMDAR blockade does not augment the sprouting induced by this later lesion. However, when combined with simultaneous ablation of the ipsilateral visual cortex, P10/P11 lesions show increased sprouting after NMDAR blockade. These data indicate that P0 NMDAR blockade does not eliminate synaptic competition in the sSC. Instead, early elimination of NMDAR function appears to facilitate sprouting that is gated in a stepwise manner by the other visual afferents.