Effects of atipamezole on selected physiologic parameters in cynomolgus macaques (Macaca fascicularis).

BACKGROUND: Atipamezole, an α-2 adrenergic receptor antagonist, reverses the α-2 agonist anesthetic effects. There is a dearth of information on the physiological effects of these drugs in cynomolgus macaques (Macaca fascicularis). We assessed atipamezole's physiologic effects. We hypothesized atipamezole administration would alter anesthetic parameters. METHODS: Five cynomolgus macaques were sedated with ketamine/dexmedetomidine intramuscularly, followed 45 min later with atipamezole (0.5 mg/kg). Anesthetic parameters (heart rate, blood pressure [systolic (SAP), diastolic (DAP), and mean (MAP) blood pressure], body temperature, respiratory rate, and %SpO2) were monitored prior to and every 10 min (through 60 min) post atipamezole injection. RESULTS: While heart rate was significantly increased for 60 min; SAP, DAP, MAP, and temperature were significantly decreased at 10 min. CONCLUSIONS: This study indicates subcutaneous atipamezole results in increased heart rate and transient blood pressure decrease. These findings are clinically important to ensure anesthetist awareness to properly support and treat patients as needed.

Disección endoscópica submucosa para el tratamiento del cáncer esofágico / Endoscopic submucosal dissection for the treatment of esophageal cancer

Resumen Introducción: El cáncer de esófago (CE) constituye la sexta causa de muerte por cáncer en el mundo. La disección endoscópica submucosa (DES) es una técnica que permite la resección en bloque de lesiones del tubo digestivo. Tiene rol curativo en pacientes seleccionados y potenciales ventajas sobre la esofagectomía. Objetivo: Describir los resultados perioperatorios y oncológicos de la DES como tratamiento del CE en nuestro centro. Materiales y Método: Estudio retrospectivo de pacientes sometidos a DES por CE entre los años 2010-2020. Resultados: Diez pacientes fueron tratados con DES por CE entre los años 2010 y 2020. El 80% eran hombres y la edad promedio fue de 72 años (63-84). La resección en bloque fue lograda en todos los casos y no se presentó morbimortalidad perioperatoria. Todas las disecciones fueron R0 y el 90% cumplió con estándares de curación. El seguimiento promedio fue de 38 meses (3,5-123). La sobrevida global fue de 90%. La sobrevida específica por cáncer y libre de recurrencia fue de 100%. Discusión: La morbimortalidad asociada a la esofagectomía es alta. La DES sería una alternativa más segura, que permite lograr un R0 y eventualmente la curación en pacientes seleccionados con CE limitado a la mucosa o submucosa. Conclusión: La presente constituye la primera serie reportada de pacientes con cáncer esofágico sometidos a DES en nuestro país. Muestra excelentes resultados oncológicos y seguridad del procedimiento, comparables a las grandes series descritas en la literatura internacional.

Introduction: Esophageal cancer is the sixth leading cause of death by cancer worldwide. Endoscopic submucosal dissection (ESD) is a technique that allows en bloc resection of early lesions of the digestive tract. It has curative potential in selected patients and potential benefits over esophagectomy for the treatment of esophageal cancer (EC). Aim: To report the results of ESD for EC in a high-volume center in Chile. Materials and Method: Retrospective descriptive study of patients who underwent ESD for EC at our center. Results: A total of 10 patients were treated with ESD for EC between 2010 and 2020. Eighty percent were male patients, the average age was 72 years (63-84). En bloc resection was achieved in all cases and there were no complications or mortality. All of the dissections were classified as R0 and 90% met curative standards. The mean follow-up was 38 months (3.5-123). Overall survival was 90%. Cancer-specific survival was 100% and recurrence-free survival was 100%. Discussion: The rate of morbidity and mortality of esophagectomy is high. ESD would be a safer technique, which allows R0 resections and eventually curation in selected patients with EC limited to the mucosa or submucosa. Conclusion: This is the first report of ESD for the treatment of EC in our country, it shows excellent oncologic results and safety of the procedure, comparable to those reported in the larger series published to date.

Key Aspects of Neurovascular Control Mediated by Specific Populations of Inhibitory Cortical Interneurons.

Inhibitory interneurons can evoke vasodilation and vasoconstriction, making them potential cellular drivers of neurovascular coupling. However, the specific regulatory roles played by particular interneuron subpopulations remain unclear. Our purpose was therefore to adopt a cell-specific optogenetic approach to investigate how somatostatin (SST) and neuronal nitric oxide synthase (nNOS)-expressing interneurons might influence the neurovascular relationship. In mice, specific activation of SST- or nNOS-interneurons was sufficient to evoke hemodynamic changes. In the case of nNOS-interneurons, robust hemodynamic changes occurred with minimal changes in neural activity, suggesting that the ability of blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) to reliably reflect changes in neuronal activity may be dependent on type of neuron recruited. Conversely, activation of SST-interneurons produced robust changes in evoked neural activity with shallow cortical excitation and pronounced deep layer cortical inhibition. Prolonged activation of SST-interneurons often resulted in an increase in blood volume in the centrally activated area with an accompanying decrease in blood volume in the surrounding brain regions, analogous to the negative BOLD signal. These results demonstrate the role of specific populations of cortical interneurons in the active control of neurovascular function.

Improving wheat as a source of iron and zinc for global nutrition.

Wheat is the staple food crop in temperate countries and increasingly consumed in developing countries, displacing traditional foods. However, wheat products are typically low in bioavailable iron and zinc, contributing to deficiencies in these micronutrients in countries where wheat is consumed as a staple food. Two factors contribute to the low contents of bioavailable iron and zinc in wheat: the low concentrations of these minerals in white flour, which is most widely consumed, and the presence of phytates in mineral-rich bran fractions. Although high zinc types of wheat have been developed by conventional plant breeding (biofortification), this approach has failed for iron. However, studies in wheat and other cereals have shown that transgenic (also known as genetically modified; GM) strategies can be used to increase the contents of iron and zinc in white flour, by converting the starchy endosperm tissue into a 'sink' for minerals. Although such strategies currently have low acceptability, greater understanding of the mechanisms which control the transport and deposition of iron and zinc in the developing grain should allow similar effects to be achieved by exploiting naturally induced genetic variation. When combined with conventional biofortification and innovative processing, this approach should provide increased mineral bioavailability in a range of wheat products, from white flour to wholemeal.

Structure determination and crystal chemistry of large repeat mixed-layer hexaferrites.

Hexaferrites are an important class of magnetic oxides with applications in data storage and electronics. Their crystal structures are highly modular, consisting of Fe- or Ba-rich close-packed blocks that can be stacked in different sequences to form a multitude of unique structures, producing large anisotropic unit cells with lattice parameters typically >100 Šalong the stacking axis. This has limited atomic-resolution structure solutions to relatively simple examples such as Ba2Zn2Fe12O22, whilst longer stacking sequences have been modelled only in terms of block sequences, with no refinement of individual atomic coordinates or occupancies. This paper describes the growth of a series of complex hexaferrite crystals, their atomic-level structure solution by high-resolution synchrotron X-ray diffraction, electron diffraction and imaging methods, and their physical characterization by magnetometry. The structures include a new hexaferrite stacking sequence, with the longest lattice parameter of any hexaferrite with a fully determined structure.

Enhancing mineral bioavailability from cereals: Current strategies and future perspectives.

Inadequate intake of essential minerals such as iron and zinc is a public health concern in the UK, particularly for girls and young women. Approximately 30% and 50% of the zinc and iron, respectively, in the UK diet is provided by cereals. In wheat, most of the iron and zinc is contained within the aleurone cell layer; however, aleurone is removed during processing of wheat into white flour. While elemental iron powder is added back into white flour at the milling stage, there is no restoration of zinc. Elemental iron powder has very low bioavailability, and therefore, in our current Biotechnology and Biological Sciences Research Council Diet and Health Research Industry Club-funded project, we are investigating the potential use of aleurone as a bioavailable source of minerals that could be added to wheat-based foods. This work has relevance for the food industry and may establish the use of aleurone as a functional food ingredient for fortification of a range of cereal-based food products.

Characteristics of MR Neuroimaging Services Billed by Radiologists versus Nonradiologists.

BACKGROUND AND PURPOSE: Although most neuroimaging examinations are interpreted by radiologists, many nonradiologists provide interpretation services. We studied day of the week, site of service, and patient complexity differences for common Medicare MR neuroimaging examinations interpreted by radiologists versus nonradiologists. MATERIALS AND METHODS: Using carrier claims files for a 5% sample of Medicare beneficiaries from 2012 to 2014, we identified all claims for brain and lumbar spine MR imaging examinations. Services were categorized by physician specialty, day of the week, and the site of service. Patient complexity was calculated using Charlson Comorbidity Indices. The χ2 was performed to test statistical significance. RESULTS: A provider specialty could be identified for 568,423 brain and lumbar spine MR imaging examinations. Of weekday examinations, radiologists interpreted 475,288 (92.3%), and nonradiologists, 39,510 (7.7%). Of weekend examinations, radiologists interpreted 52,028 (97.0%) and nonradiologists 1597 (3.0%). Radiologists interpreted 145,904 (98.7%) examinations in the inpatient hospital and emergency department settings versus 1882 (1.3%) by nonradiologists. Of all examinations, 44,547 of those interpreted by radiologists (8.4%) were on the most clinically complex patients versus 2139 (5.2%) for nonradiologists. All interspecialty differences for day of the week, the site of service, and patient complexity were statistically significant (P < .001). CONCLUSIONS: Although radiologists interpret most common MR neuroimaging examinations for Medicare beneficiaries, in contrast to nonradiologists, they disproportionately render those services on weekends, in higher acuity sites, and on more complex patients. To optimize access and minimize disparities in necessary neuroimaging, quality metrics should consider such service characteristics.

Crush injury to motor nerves in the G93A transgenic mouse model of amyotrophic lateral sclerosis promotes muscle reinnervation and survival of functionally intact nerve-muscle contacts.

Selective survival of small motor nerve fibers and their neuromuscular contacts in the SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis (ALS) suggests that smaller regenerated nerve fibers are more able to sustain reformed nerve-muscle connections as functionally intact motor units (MUs). The sciatic nerve was crushed unilaterally in SOD1G93A transgenic mice at 40 days of age and contractile forces of reinnervated muscles and their MUs were recorded at 90 days in order to determine the capacities of the nerves to regenerate and to form and retain functional neuromuscular connections. Reduced MU numbers in fast-twitch tibialis anterior, extensor digitorum longus and medial gastrocnemius muscles and the lesser reductions in slow-twitch soleus muscle of SOD1G93A transgenic mice were reversed in reinnervated muscles: there were more reinnervated MUs and their contractile forces and the muscle forces and weights increased. In line with the contrasting ability of only small not large nerve fibers to sprout to form enlarged MUs in the SOD1G93A transgenic mouse, the smaller regenerating nerve fibers formed enlarged MUs that were better able to survive. Because nerve fibers with and without muscle contacts were severed by the sciatic nerve crush injury, the conditioning lesion is untenable as the explanation for improved maintenance of reinnervated neuromuscular junctions. Elevated neurotrophic factor expression in axotomized motoneurons and/or denervated Schwann cells and the synapse withdrawal from axotomized motoneurons are other factors that, in addition to reduced size of nerve fibers reinnervating muscles, may account for increased survival and size of reinnervated MUs in ALS.

Diurnal and photoperiodic changes in thyrotrophin-stimulating hormone ß expression and associated regulation of deiodinase enzymes (DIO2, DIO3) in the female juvenile chicken hypothalamus.

Increased thyrotrophin-stimulating hormone ß (TSHß) expression in the pars tuberalis is assumed to be an early step in the neuroendocrine mechanism transducing photoperiodic information. The present study aimed to determine the relationship between long-photoperiod (LP) and diurnal TSHß gene expression in the juvenile chicken by comparing LP-photostimulated birds with groups kept on a short photoperiod (SP) for 1 or 12 days. TSHß expression increased by 3- and 23-fold after 1 and 12 days of LP-photostimulation both during the day and at night. Under both SP and LP conditions, TSHß expression was between 3- and 14-fold higher at night than in the day, suggesting that TSHß expression cycles in a diurnal pattern irrespective of photoperiod. The ratio of DIO2/3 was decreased on LPs, consequent to changes in DIO3 expression, although there was no evidence of any diurnal effect on DIO2 or DIO3 expression. Plasma prolactin concentrations revealed both an effect of LPs and time-of-day. Thus, TSHß expression changes in a dynamic fashion both diurnally and in response to photoperiod.

Miotomía endoscópica por vía oral (POEM) para el tratamiento de la acalasia: experiencia clínica inicial y resultados a corto plazo / Per-oral endoscopic myotomy (POEM) for the treatment of achalasia: initial clinical experience and short term results

Resumen Introducción: La acalasia es el trastorno motor primario más frecuente del esófago. El estándar de tratamiento actual es la miotomía de Heller laparoscópica. En los últimos años, el desarrollo de técnicas endoscópicas avanzadas ha permitido el posicionamiento de la técnica POEM (del inglés: per-oral endoscopic myotomy) como una nueva alternativa terapéutica con resultados promisorios. Objetivo: Presentar nuestra experiencia clínica, con descripción de la técnica utilizada, resultados perioperatorios y seguimiento a corto plazo en el desarrollo de esta alternativa terapéutica. Materiales y métodos: Se realizó un análisis retrospectivo de datos obtenidos en forma prospectiva de 15 pacientes intervenidos mediante POEM en 3 hospitales docentes asociados. Se recopilaron variables demográficas preoperatorias, detalle del intraoperatorio y registro de morbimortalidad operatoria. Se realizó un seguimiento clínico dirigido registrando el puntaje de Eckardt y la presencia de síntomas de reflujo gastroesofágico. Resultados: Entre agosto de 2015 y noviembre de 2016 se realizaron 15 POEM. Seis de estos pacientes eran mujeres, y la edad promedio fue de 49 años. El tiempo operatorio promedio fue de 110 min; no hubo morbimortalidad operatoria. La estadía hospitalaria promedio fue de 2,8 días. El seguimiento fue de entre 1 y 15 meses. El puntaje de Eckardt promedio en el preoperatorio y en el postoperatorio fue de 10,5 y 0,4 puntos, respectivamente. Tres pacientes presentaban síntomas de reflujo gastroesofágico al momento del seguimiento. Conclusión: Los resultados obtenidos en nuestra serie apoyan la efectividad y seguridad del POEM a corto plazo. Se requiere de un seguimiento mayor para determinar el rol definitivo de esta técnica.

Abstract Introduction: Achalasia is the most common primary motor disorder of the esophagus. The current standard of treatment is laparoscopic Heller's myotomy. Recently the development of advanced endoscopic techniques has allowed the positioning of the POEM (per-oral endoscopic myotomy) technique as a new therapeutic alternative with promising results. Objective: To present our clinical experience in POEM, with description of the technique used, peri-operative results and short-term follow-up in the development of this therapeutic alternative. Materials and methods: We performed a retrospective analysis of data obtained prospectively from 15 patients undergoing POEM in three clinical centers in our country. Preoperative demographic variables, intraoperative detail, and operative morbidity and mortality were collected. Clinical follow-up was performed with controls recording Eckardt score and presence of gastroesophageal reflux symptoms. Results: Between August 2015 and November 2016, 15 POEM were performed, six of these patients were women, average age was 49 years. The average operative time was 110 min, we did not have any perioperative morbimortality. Hospital stay was 2.8 days. Follow-up was between 1 and 15 months, Eckardt's preoperative and postoperative score was on average 10.5 and 0.4 points, respectively. Three patients had gastroesophageal reflux symptoms at the time of follow-up. Conclusion: Our results support the effectiveness and security of POEM in short-term follow up. Further monitoring is required to determine the definitive role of this technique.

Review: Neuropathology and behavioural features of transgenic murine models of Alzheimer's disease.

Our understanding of the underlying biology of Alzheimer's disease (AD) has been steadily progressing; however, this is yet to translate into a successful treatment in humans. The use of transgenic mouse models has helped to develop our understanding of AD, not only in terms of disease pathology, but also with the associated cognitive impairments typical of AD. Plaques and neurofibrillary tangles are often among the last pathological changes in AD mouse models, after neuronal loss and gliosis. There is a general consensus that successful treatments need to be applied before the onset of these pathologies and associated cognitive symptoms. This review discusses the different types of AD mouse models in terms of the temporal progression of the disease, how well they replicate the pathological changes seen in human AD and their cognitive defects. We provide a critical assessment of the behavioural tests used with AD mice to assess cognitive changes and decline, and discuss how successfully they correlate with cognitive impairments in humans with AD. This information is an important tool for AD researchers when deciding on appropriate mouse models, and when selecting measures to assess behavioural and cognitive change.

Leveraging Industry-Academia Collaborations in Adaptive Biomedical Innovation.

Despite the rapid pace of biomedical innovation, research and development (R&D) productivity in the pharmaceutical industry has not improved broadly. Increasingly, firms need to leverage new approaches to product development and commercial execution, while maintaining adaptability to rapid changes in the marketplace and in biomedical science. Firms are also seeking ways to capture some of the talent, infrastructure, and innovation that depends on federal R&D investment. As a result, a major transition to external innovation is taking place across the industry. One example of these external innovation initiatives is the Sanofi-MIT Partnership, which provided seed funding to MIT investigators to develop novel solutions and approaches in areas of interest to Sanofi. These projects were highly collaborative, with information and materials flowing both ways. The relatively small amount of funding and short time frame of the awards built an adaptable and flexible process to advance translational science.

The development of peer reflective supervision amongst nurse educator colleagues: An action research project.

This action research study developed the use of peer reflective supervision (PRS) amongst eight nurse educators contributing to an undergraduate Adult Nursing programme at a UK University. During the academic year (2013-14), nurse educator co-researchers met for an introductory workshop and then met regularly in pairs to facilitate each other's reflection. This provided an opportunity for nurse educators to reflect on identified issues linked to their role with a facilitative peer. Educators met three additional times in a Reflexive Learning Group (RLG), to gather data on their use of PRS. Audio-recordings from the RLGs were transcribed and analysed using Norton's (2009) thematic analysis framework. Co-researchers iteratively validated the data and an external validation group critically viewed the evidence. Overall, seven themes were generated from the three research cycles. These were: PRS as a Valuable Affirming Experience; Time Issues; Facilitation- Support, Trust and Challenge; Developing a Flexible 'Toolbox'; To Write or Not to Write; Drawing on Literature; and Requirement for Action. Findings add new evidence regarding use of a flexible toolbox of resources to develop reflection and offer practical guidance on the development of PRS. Nurse educators often experienced similar concerns, and a facilitative supervision structure allowed co-researchers to positively explore these. Recognition of work pressures and requirement for time and space for reflection was highlighted, particularly regarding writing, and exploring the literature, to develop critical analysis of experiences. The importance of action as part of the reflective process was emphasised. Co-researchers reported positive personal change as well as the opportunity to highlight issues through their reflection for further action within the organisation. The study adds constructive evidence for the use of reflection to explore professional work, make sense of experiences and develop positive action. It has transferability to a wider international audience interested in the development of reflection amongst colleagues and the use of insider research techniques to challenge and develop practice.

BET inhibition represses miR17-92 to drive BIM-initiated apoptosis of normal and transformed hematopoietic cells.

The BET (bromodomain and extraterminal domain) bromodomain-containing proteins, such as BRD4, are highly promising targets for treating lymphoid and myeloid malignancies. They act to modulate the expression of multiple genes that control diverse cellular processes including proliferation, survival and differentiation that are consequentially disrupted by small-molecule BET bromodomain inhibitors such as JQ1. By assessing the impact of these inhibitors on normal mouse hematopoietic cells or their transformed counterparts, we establish definitively that their cytotoxic action in vitro and in vivo relies predominantly on the activation of BAX/BAK-dependent mitochondrial (intrinsic) apoptosis. In large part, this is triggered by marked upregulation of the BH3-only protein BIM when the BET inhibitors suppress miR-17-92, a key post-transcriptional repressor of BIM expression. Thus, our study strongly suggests that mutations that permit the evasion of apoptosis (for example, BCL2 overexpression, BIM inactivation) are likely to blunt the activity of the BET bromodomain inhibitors and should be anticipated when therapy resistance develops. Strikingly, we also found that certain normal hematopoietic cells, especially those of lymphoid origin, are as prone to apoptosis induced by the BET inhibitors as their transformed counterparts, indicating that their susceptibility to BET inhibitors did not arise from oncogenic transformation.

Micromilling enhances iron bioaccessibility from wholegrain wheat.

Cereals constitute important sources of iron in human diet; however, much of the iron in wheat is lost during processing for the production of white flour. This study employed novel food processing techniques to increase the bioaccessibility of naturally occurring iron in wheat. Iron was localized in wheat by Perl's Prussian blue staining. Soluble iron from digested wheat flour was measured by a ferrozine spectrophotometric assay. Iron bioaccessibility was determined using an in vitro simulated peptic-pancreatic digestion, followed by measurement of ferritin (a surrogate marker for iron absorption) in Caco-2 cells. Light microscopy revealed that iron in wheat was encapsulated in cells of the aleurone layer and remained intact after in vivo digestion and passage through the gastrointestinal tract. The solubility of iron in wholegrain wheat and in purified wheat aleurone increased significantly after enzymatic digestion with Driselase, and following mechanical disruption using micromilling. Furthermore, following in vitro simulated peptic-pancreatic digestion, iron bioaccessibility, measured as ferritin formation in Caco-2 cells, from micromilled aleurone flour was significantly higher (52%) than from whole aleurone flour. Taken together our data show that disruption of aleurone cell walls could increase iron bioaccessibility. Micromilled aleurone could provide an alternative strategy for iron fortification of cereal products.

Prevención de la recurrencia peritoneal en el tratamiento quirúrgico del cáncer gástrico / Prevention of peritoneal recurrence of gastric cancer

The peritoneal cavity is the main site of gastric cancer recurrence after curative surgery. When this recurrence occurs, patients may experience bowel obstruction, dehydration and multiple hospital admissions. The therapeutic options that may decrease the rate of peritoneal recurrence and increase five years survival are intraoperative hyperthermic chemotherapy, extensive intraoperative peritoneal lavage and routine bursectomy. We herein review the oncological results of curative surgery for gastric cancer, its failure patterns and the risk factors for peritoneal recurrence. We also review the studies aiming to prevent peritoneal carcinomatosis.

La recurrencia peritoneal en el cáncer gástrico avanzado, luego de una cirugía con intención curativa es un problema que debe ser considerado una prioridad en nuestro país, debido a la alta proporción de pacientes con compromiso de la serosa gástrica al momento del diagnóstico, siendo el peritoneo el principal sitio de recurrencia luego de una cirugía con intención curativa en este grupo. Luego de la recurrencia peritoneal, los pacientes presentan un deterioro importante de la calidad de vida, principalmente por episodios de obstrucción intestinal, deshidratación y rehospitalizaciones. Se han realizado múltiples estudios en el extranjero de potenciales medidas que se pueden realizar durante la cirugía inicial con intención curativa que previenen la recurrencia. Algunas de estas medidas han disminuido la recurrencia peritoneal y aumentado la sobrevida a 5 años, como son la quimioterapia hipertérmica intraoperatoria, el lavado peritoneal extensivo y la bursectomía rutinaria, en pacientes seleccionados. El objetivo de la presente revisión es mostrar los resultados oncológicos de la cirugía curativa, los patrones de falla luego de una cirugía curativa, los factores de riesgo para una recurrencia peritoneal y los estudios que se han realizado en relación a la prevención de la carcinomatosis peritoneal.

Subdominant hierarchical ovarian follicles are needed for steroidogenesis and ovulation in laying hens (Gallus domesticus).

Ovarian follicle development in avian species is characterized by a strict hierarchical arrangement. The hierarchical follicles secrete progesterone, which induces the LH surge, but the capacity to produce other steroids decreases with development. Our aim was to evaluate the complementary action of subdominant follicles (F4-F6) on ovulation and steroidogenesis of the preovulatory follicles (F1-F3) in domestic laying hens. The first study included four groups: control (C); sham-operated (SO); large hierarchical follicles (LHF) from which F4-F6 follicles were extracted; and subdominant hierarchical follicles (SHF) from which F1-F3 follicles were extracted. Blood samples were collected every 2h from 12h before estimated ovoposition until 2h after ovoposition. Egg laying continued at the same rates in C and SO hens, with normal preovulatory surges of oestradiol, testosterone, progesterone and LH. In contrast, in LHF and SHF groups, ovoposition was blocked; oestradiol concentrations were not affected; but no preovulatory surges of testosterone, progesterone or LH were seen. Further, the testosterone surge was required for the occurrence of progesterone and LH surges. In the second study StAR and steroidogenic enzyme mRNA expression was evaluated within F1-F3 follicles from a LHF group and C-14 and C-8 controls groups, in which follicles were collected 14h and 8h before expected ovoposition, respectively. Extraction of F4-F6 follicles caused a significant reduction in StAR and 3ß-HSD expressions within theca, but not in granulosa cells. In conclusion, subdominant hierarchical follicles (F4-F6) are required for the preovulatory release of testosterone, progesterone and LH, which are highly inter-correlated.

Acute abdominal pain and constipation due to lead poisoning.

Although uncommon, lead poisoning should be considered as a differential diagnosis in cases of unexplained acute abdominal pain in both adults and children. We present the case of a 35-year-old Asian male who presented with abdominal pain and constipation secondary to lead poisoning. Initially, the source of lead exposure was not apparent; this was later found to be due to ingestion of an Ayurvedic herbal medicine for the treatment of infertility. Lead poisoning due to the ingestion of Ayurvedic remedies is well described. We discuss the diagnosis, pathophysiology and treatment of lead poisoning. This case illustrates one of the rarer medical causes of acute abdominal pain and emphasizes the need to take a thorough history (including specific questioning regarding the use of over-the-counter and traditional/ herbal remedies) in cases of suspected poisoning or drug toxicity.

Improving the economic value of photographic screening for optical coherence tomography-detectable macular oedema: a prospective, multicentre, UK study.

OBJECTIVES: To determine the best photographic surrogate markers for detecting sight-threatening macular oedema (MO) in people with diabetes attending UK national screening programmes. DESIGN: A multicentre, prospective, observational cohort study of 3170 patients with photographic signs of diabetic retinopathy visible within the macular region [exudates within two disc diameters, microaneurysms/dot haemorrhages (M/DHs) and blot haemorrhages (BHs)] who were recruited from seven study centres. SETTING: All patients were recruited and imaged at one of seven study centres in Aberdeen, Birmingham, Dundee, Dunfermline, Edinburgh, Liverpool and Oxford. PARTICIPANTS: Subjects with features of diabetic retinopathy visible within the macular region attending one of seven diabetic retinal screening programmes. INTERVENTIONS: Alternative referral criteria for suspected MO based on photographic surrogate markers; an optical coherence tomographic examination in addition to the standard digital retinal photograph. MAIN OUTCOME MEASURES: (1) To determine the best method to detect sight-threatening MO in people with diabetes using photographic surrogate markers. (2) Sensitivity and specificity estimates to assess the costs and consequences of using alternative strategies. (3) Modelled long-term costs and quality-adjusted life-years (QALYs). RESULTS: Prevalence of MO was strongly related to the presence of lesions and was roughly five times higher in subjects with exudates or BHs or more than two M/DHs within one disc diameter. Having worse visual acuity was associated with about a fivefold higher prevalence of MO. Current manual screening grading schemes that ignore visual acuity or the presence of M/DHs could be improved by taking these into account. Health service costs increase substantially with more sensitive/less specific strategies. A fully automated strategy, using the automated detection of patterns of photographic surrogate markers, is superior to all current manual grading schemes for detecting MO in people with diabetes. The addition of optical coherence tomography (OCT) to each strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. CONCLUSIONS: Compared with all current manual grading schemes, for the same sensitivity, a fully automated strategy, using the automated detection of patterns of photographic surrogate markers, achieves a higher specificity for detecting MO in people with diabetes, especially if visual acuity is included in the automated strategy. Overall, costs to the health service are likely to increase if more sensitive referral strategies are adopted over more specific screening strategies for MO, for only very small gains in QALYs. The addition of OCT to each screening strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. STUDY REGISTRATION: This study has been registered as REC/IRAS 07/S0801/107, UKCRN ID 9063 and NIHR HTA 06/402/49. SOURCE OF FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 51. See the HTA programme website for further project information.

Endocrine phenotype, reproductive success and survival in the great tit, Parus major.

A central goal in evolutionary ecology is to characterize and identify selection patterns on the optimal phenotype in different environments. Physiological traits, such as hormonal responses, provide important mechanisms by which individuals can adapt to fluctuating environmental conditions. It is therefore expected that selection shapes hormonal traits, but the strength and the direction of selection on plastic hormonal signals are still under investigation. Here, we determined whether, and in which way, selection is acting on the hormones corticosterone and prolactin by characterizing endocrine phenotypes and their relationship with fitness in free-living great tits, Parus major. We quantified variation in circulating concentrations of baseline and stress-induced corticosterone and in prolactin during the prebreeding (March) and the breeding season (May) for two consecutive years, and correlated these with reproductive success (yearly fledgling number) and overwinter survival in female and male individuals. In both years, individuals with high baseline corticosterone concentrations in March had the highest yearly fledgling numbers; while in May, individuals with low baseline corticosterone had the highest yearly reproductive success. Likewise, individuals that displayed strong seasonal plasticity in baseline corticosterone concentrations (high in March and low in May) had the highest reproductive success in each year. Prolactin concentrations were not related to reproductive success, but were positively correlated to the proximity to lay. Between-year plasticity in stress-induced corticosterone concentrations of males was related to yearly variation in food abundance, but not to overall reproductive success. These findings suggest that seasonally alternating directional selection is operating on baseline corticosterone concentrations in both sexes. The observed between-year consistency in selection patterns indicates that a one-time hormone sample in a given season can allow the prediction of individual fitness.