Fractionated stereotactic radiotherapy in the treatment of pituitary adenomas.

PURPOSE: The purpose of this work was to evaluate tumor control and side effects associated with fractionated stereotactic radiotherapy (FSRT) in the management of residual or recurrent pituitary adenomas. PATIENTS AND METHODS: We report on 37 consecutive patients with pituitary adenomas treated with FSRT at our department. All patients had previously undergone surgery. Twenty-nine patients had nonfunctioning, 8 had hormone-producing adenoma. The mean total dose delivered by a linear accelerator was 49.4 Gy (range 45-52.2 Gy), 5 × 1.8 Gy weekly. The mean PTV was 22.8 ccm (range 2.0-78.3 ccm). Evaluation included serial imaging tests, endocrinologic and ophthalmologic examination. RESULTS: Tumor control was 91.9 % for a median follow-up time of 57 months (range 2-111 months). Before FSRT partial hypopituitarism was present in 41 % of patients, while 35 % had anterior panhypopituitarism. After FSRT pituitary function remained normal in 22 %, 43 % had partial pituitary dysfunction, and 35 % had anterior panhypopituitarism. Visual acuity was stable in 76 % of patients, improved in 19 %, and deteriorated in 5 %. Visual fields remained stable in 35 patients (95 %), improved in one and worsened in 1 patient (2.7 %). CONCLUSION: FSRT is an effective and safe treatment for recurrent or residual pituitary adenoma. Good local tumor control and preservation of adjacent structures can be reached, even for large tumors.

Successional colonization of perennial ryegrass by rumen bacteria.

UNLABELLED: This study investigated successional colonization of perennial ryegrass (PRG) by the rumen microbiota. PRG grown for 6 weeks in a greenhouse was incubated in sacco in the rumens of three Holstein × Freisian cows over a period of 24 h. PRG incubated within the rumen was subsequently harvested at various time intervals postincubation to assess colonization over time. DGGE-based dendograms revealed the presence of distinct primary (0-2 h) and secondary (4 h onwards) attached bacterial communities. Moving window analysis, band number and Shannon-Wiener diversity indices suggest that after 2 h a proportion of primary colonizing bacteria detach, to be replaced with a population of secondary colonizing bacteria between 2 and 4 h after entry of PRG into the rumen. Sequencing and classification of bands lost and gained between 2 and 4 h showed that the genus Prevotella spp. was potentially more prevalent following 4 h of incubation, and Prevotella spp. 16S rDNA-based QPCR supported this finding somewhat, as 2- to 4-h Prevotella QPCR data were greater but not significantly so. Low-temperature scanning electron microscopy showed that attached bacteria were predominantly enveloped in extracellular polymeric substances. In conclusion, colonization of fresh PRG is biphasic with primary colonization completed within 2 h and secondary colonization commencing after 4 h of attachment in this study. SIGNIFICANCE AND IMPACT OF THE STUDY: We investigated, over a 24-h period in sacco, whether attachment of rumen microbiota to perennial ryegrass (PRG) showed successional changes in diversity. Knowledge of the bacterial species that attach to PRG over time may aid our understanding of the temporal function of the attached microbiota and ultimately permit the development of novel strategies for improving animal production to meet the future demands for meat and milk.

27†Chiasmal misrouting in infantile nystagmus syndrome (INS): phenotypes in patients with molecular diagnoses.

Chiasmal misrouting, once believed to be pathognomonic for albinism, has been reported in cases of INS, independent of melanin pathway disruption. The purpose of this study is to determine if there are clinical-electrophysiological parameters that correlate with particular genotypes in INS.A retrospective chart review at Moorfields Eye Hospital identified 71 patients with a molecular diagnosis relating to INS. Visual acuity; presence of nystagmus, signs of albinism and OCT foveal hypoplasia grade were recorded alongside flash and pattern VEP (Visual Evoked Potential) amplitude and peak time. VEP asymmetry was assessed using the Pearson Correlation Coefficient (r).Pathological variants in 8 genes (TYR, OCA2, HPS6, HPS3, HPS1, GPR143, FRMD7, SLC38A8, OCA1) were identified. Mean BCVA per group ranged from 0.38-0.74LogMAR F(0.72,3.5)=2.8; p=0.04 one-way ANOVA. All genotypes demonstrated foveal hypoplasia (mode grade 4) except FRMD7 (all grade 1). In this cohort, positive flash and pattern VEP amplitude/peak time asymmetry correlated with clinical signs of albinism (flash VEP, r=0.22(0-6yrs); pattern VEP, r=0.17(6-65yrs)). There was marked asymmetry in SLC38A8 patients (r = -0.85 to-0.93), a feature known to be associated with foveal hypoplasia 2.This study provides a detailed genotype-phenotype correlation of VEP findings in a molecularly characterised INS cohort - useful in selecting clinically guided genetic testing and counselling patients.

Conflict management in public hospitals: the Cyprus case.

BACKGROUND: Conflict among health-care personnel has been identified as an issue within health-care settings around the world. AIM: To investigate the existence and management of conflict among health-care personnel in public hospitals in Cyprus; to assess the factors leading to conflict among staff members; to evaluate the consequences of conflict arising; and to consider the management strategies. METHODS: A self-administered questionnaire was completed by a random sample of 1037 health-care professionals in all (seven) state-run hospitals in Cyprus in 2008. RESULTS: Mean age of respondents was 41 years, and 75% were female. Sixty-four per cent of respondents reported that they had never been informed about conflict management strategies, with physicians being the least informed as the relative percentage was 79.8% (χ(2) = 33, P < 0.001). Sixty per cent of health-care professionals reported conflict at work with other health-care personnel one to five times per week, and 37% of the respondents stated that they devote 90 min (mean value) from work during their shift in conflict resolution, meaning that managing conflicts may absorb 19% of working time daily. The majority of respondents agreed that organizational problems and communication gaps were the main issues creating conflict. Avoidance and collaboration were the preferable strategies for conflict resolution, used by 36.6% and 37.5% of the respondents, respectively. CONCLUSION: Better communication, fair management practices and clear job descriptions and expectations may be needed in order to facilitate change and reverse the negative atmosphere that exists. Further education in conflict management for physicians, nurses and their managers may also be needed.

Bio-processing of macroalgae Palmaria palmata: metabolite fractionation from pressed fresh material and ensiling considerations for long-term storage.

Red algae, belonging to the phylum Rhodophyta, contain an abundance of useful chemicals including bioactive molecules and present opportunities for the production of different products through biorefinery cascades. The rhodophyte Palmaria palmata, commonly termed dulse or dillisk, grows predominantly on the northern coasts of the Atlantic and Pacific Oceans and is a well-known snack food. Due to its abundance, availability and cultivation capacity, P. palmata was selected for study as a potential candidate for a biorefinery process. In addition to studying juice and solid fractions of freshly harvested P. palmata, we have investigated the novel possibility of preserving algal biomass by ensilaging protocols similar to those employed for terrestrial forage crops. In the metabolite partitioning within the solid and liquid fractions following screw-pressing, the majority of the metabolites screened for-water soluble carbohydrates, proteins and amino acids, lipids, pigments, phenolics and antioxidant activity-remained in the solid fraction, though at differing proportions depending on the metabolite, from 70.8% soluble amino acids to 98.2% chlorophyll a and 98.1% total carotenoids. For the ensiling study, screw-pressed P. palmata, with comparative wilted and chopped, and chopped only samples, were ensiled at scale with and without Safesil silage additive. All samples were successfully ensiled after 90 days, with screw-pressing giving lower or equal pH before and after ensiling compared with the other preparations. Of particular note was the effluent volumes generated during ensiling: 26-49% of the fresh weight, containing 16-34% of the silage dry matter. This may be of advantage depending on the final use of the biomass.

Analysis of PIK3CA and B-RAF gene mutations in human astrocytomas: association with activation of ERK and AKT.

OBJECTIVE: The analysis of the presence of PIK3CA and B-RAF gene mutations in relation to ERK and AKT activation in diffusely infiltrating astrocytomas, in order to determine their potential role in tumor aggressiveness. METHODS: Polymerase chain reaction-single strand confirmation polymorphism (PCR-SSCP) and sequencing analysis were used for PIK3CA and B-RAF gene mutation detection. pERK and pAKT expression were examined by immunohistochemistry. RESULTS: PIK3CA mutations were found in 2 (3%) cases of glioblastomas whereas none of these cases displayed mutations in exon 15 of B-RAF gene. Neither low grade astrocytomas nor anaplastic astrocytomas revealed any mutations in these genes. Nuclear and cytoplasmic pERK immunoreactivity was displayed in 100% and 82% of cases, respectively. pERK nuclear expression was positively correlated with pERK cytoplasmic expression (p = 0.0067). Moreover, pERK nuclear expression increased in parallel with tumor grade (II, III v/s IV, p = 0.0262). Nuclear and cytoplasmic pAKT immunoreactivity was displayed in 97% and 100% of cases, respectively. Similarly, pAKT nuclear expression was positively correlated with pAKT cytoplasmic expression (p = 0.0074). pAKT cytoplasmic expression increased with increasing tumor grade (II,III v/s IV, p = 0.0930), although the latter relationship was of marginal significance. pAKT cytoplasmic expression was also positively correlated with pERK nuclear expression (p = 0.0156). CONCLUSIONS: Our study reports the low frequency of PIK3CA and B-RAF mutations in astrocytomas, despite the presence of activated ERK and AKT proteins. Moreover, the correlation of pERK nuclear and pAKT cytoplasmic expression with tumor grade suggests the possible crucial role of the activation of these proteins in human gliomagenesis.

Evolving trends in strabismus following retinal surgery: is there still a role for botulinum toxin?

Purpose Ocular motility disturbances following retinal detachment surgery are well documented, resulting in ocular misalignment and disabling diplopia. Interestingly, there has been a downward trend over the last decade across the United Kingdom with the evolution of refined vitrectomy techniques and instrumentation. We aim to report our updated experience on factors influencing botulinum toxin outcomes in view of the trend toward vitrectomy. Methods The Moorfields strabismus service carried out a follow-up retrospective study of all subjects that received botulinum toxin for retinal surgery-related strabismus at our center over an eleven-year period. All new onset constant or intermittent strabismus following retinal detachment surgery were included. Botulinum toxin response was stratified to good and poor. Results 32 patients fulfilled our criteria, with a mean follow-up of 20 months. The majority were vitrectomised eyes (62%), presented with diplopia (60%) and exotropia (66%). All isolated and combined vertical deviations (18%) were noted among cryobuckled eyes only. Baseline largest mean horizontal deviation was 49 and 51 prism diopters (PD) among the good and poor responders, respectively. A statistically and clinically significant reduction in the horizontal angle of deviation was noted among the good (p < .0001) responders, requiring a mean of six injections, in comparison to the poor responders (p = .03). Of the good responders, five patients (16%) with decompensated phorias regained fusion control. A small number of complications (15%) were noted, the most marked being intractable diplopia in a good responder (3%) with failure to fuse. Conclusions Botulinum toxin is a useful treatment modality, particularly when surgical options are limited. It can restore binocularity in patients with preexisting fusion potential. Ocular cosmesis can be achieved but requires ongoing injections. Barriers to fusion restoration include multiple retinal surgeries, persistent macula pathology and central-peripheral retinal rivalry. This highlights the need for rigorous baseline macula assessment to allow a tailored approach when considering botulinum toxin therapy for strabismus.

Paediatric endophthalmitis: a UK retrospective study.

INTRODUCTION: Paediatric endophthalmitis is a severe but rare complication of intraocular surgery, penetrating trauma and far less commonly extra-ocular surgery or endogenous origin. We set out to establish the incidence and risk factors of exogenous endophthalmitis in children, and to develop an evidence-based protocol that can be used for treatment of suspected exogenous endophthalmitis in children. METHODS: Microbiology reports and operation numbers were obtained from two large tertiary referral hospitals sharing 24-h paediatric ophthalmology cover for the period January 2009-December 2016. All cases of aqueous and/or vitreous tap performed on children aged ≤18 years were identified and case notes reviewed for complete information on each case. RESULTS: Sixteen cases were eligible for inclusion as 'postoperative endophthalmitis': complete data was found on 13 cases. The incidence of postoperative endophthalmitis was 0.17% over 7 years. The mean age of presentation was 5.5 years (range from 7 months to 16 years and 9 months), from 3 days-78 months post operatively. In all, 11/13 had at least one glaucoma procedure. Microbiology results showed growth in 8/13. Most isolates were Gram-positive bacteria but Gram-negatives were also isolated and in one case Candida from a conjunctival swab. The antibiotic regime varied depending on age, organism identified and sensitivities. In all, 9/13 had hand movement or worse vision after treatment. CONCLUSION: Paediatric endophthalmitis may present to any paediatric/general ophthalmologist. It is a rare but devastating condition with poor visual prognosis, requiring prompt recognition and aggressive management. Previous glaucoma surgery is a long-term risk factor in our local paediatric population. Based on our study, an evidence-based protocol for management is proposed in order to improve outcomes.

Management of nystagmus in children: a review of the literature and current practice in UK specialist services.

Nystagmus is an eye movement disorder characterised by abnormal, involuntary rhythmic oscillations of one or both eyes, initiated by a slow phase. It is not uncommon in the UK and regularly seen in paediatric ophthalmology and adult general/strabismus clinics. In some cases, it occurs in isolation, and in others, it occurs as part of a multisystem disorder, severe visual impairment or neurological disorder. Similarly, in some cases, visual acuity can be normal and in others can be severely degraded. Furthermore, the impact on vision goes well beyond static acuity alone, is rarely measured and may vary on a minute-to-minute, day-to-day or month-to-month basis. For these reasons, management of children with nystagmus in the UK is varied, and patients report hugely different experiences and investigations. In this review, we hope to shine a light on the current management of children with nystagmus across five specialist centres in the UK in order to present, for the first time, a consensus on investigation and clinical management.

Correction: Management of nystagmus in children: a review of the literature and current practice in UK specialist services.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Supranuclear eye movements and nystagmus in children: A review of the literature and guide to clinical examination, interpretation of findings and age-appropriate norms.

Abnormal eye movements in children, including nystagmus, present a significant challenge to ophthalmologists and other healthcare professionals. Similarly, examination of supranuclear eye movements and nystagmus in children and interpretation of any resulting clinical signs can seem very complex. A structured assessment is often lacking although in many cases, simple clinical observations, combined with a basic understanding of the underlying neurology, can hold the key to clinical diagnosis. As the range of underlying diagnoses for children with abnormal eye movements is broad, recognising clinical patterns and understanding their neurological basis is also imperative for ongoing management. Here, we present a review and best practice guide for a structured, methodical clinical examination of supranuclear eye movements and nystagmus in children, a guide to clinical interpretation and age-appropriate norms. We also detail the more common specific clinical findings and how they should be interpreted and used to guide further management. In summary, this review will encourage clinicians to combine a structured assessment and a logical interpretation of the resulting clinical signs, in order to recognise patterns of presentation and avoid unnecessary investigations and protracted delays in diagnosis and clinical care.

Effect of histamine on the signal transduction of the AtoS-AtoC two component system and involvement in poly-(R)-3-hydroxybutyrate biosynthesis in Escherichia coli.

AtoS-AtoC two-component system acts directly on the atoDAEB operon transcription to regulate the biosynthesis of short-chain poly-(R)-3-hydroxybutyrate. This study sought to investigate the effect of histamine and compound 48/80 on the regulation of AtoS-AtoC two-component system in Escherichia coli K-12 MA255 (speC(-), speB(-)) and the isogenic E. coli strains BW25113 (atoSC(+)) and BW28878 (DeltaatoSC) transformed with plasmids carrying related genes. Histamine or compound 48/80 induced or tended to reduce atoC transcription, respectively, while neither compound showed any effect on atoDAEB operon transcription. Moreover, histamine down-regulated poly-(R)-3-hydroxybutyrate biosynthesis, whereas compound 48/80 up-regulated its biosynthesis, maximal induction being obtained in the presence of multiple copies of AtoS-AtoC. Interestingly, co-administration of histamine counteracted this inductive effect of compound 48/80. The reported data provide the first evidence for a differential modulator role of histamine and compound 48/80 on the AtoS-AtoC two-component system signaling in potentially pathogenic bacteria, leading to a new perspective on their symbiotic behavior.

Detection and monitoring of anaerobic rumen fungi using an ARISA method.

AIM: To develop an automated ribosomal intergenic spacer region analysis (ARISA) method for the detection of anaerobic rumen fungi and also to demonstrate utility of the technique to monitor colonization and persistence of fungi, and diet-induced changes in community structure. METHODS AND RESULTS: The method could discriminate between three genera of anaerobic rumen fungal isolates, representing Orpinomyces, Piromyces and Neocallimastix species. Changes in anaerobic fungal composition were observed between animals fed a high-fibre diet compared with a grain-based diet. ARISA analysis of rumen samples from animals on grain showed a decrease in fungal diversity with a dominance of Orpinomyces and Piromyces spp. Clustering analysis of ARISA profile patterns grouped animals based on diet. A single strain of Orpinomyces was dosed into a cow and was detectable within the rumen fungal population for several weeks afterwards. CONCLUSIONS: The ARISA technique was capable of discriminating between pure cultures at the genus level. Diet composition has a significant influence on the diversity of anaerobic fungi in the rumen and the method can be used to monitor introduced strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Through the use of ARISA analysis, a better understanding of the effect of diets on rumen anaerobic fungi populations is provided.

A standardized protocol for quantification of saccadic eye movements: DEMoNS.

OBJECTIVE: Quantitative saccadic testing is a non-invasive method of evaluating the neural networks involved in the control of eye movements. The aim of this study is to provide a standardized and reproducible protocol for infrared oculography measurements of eye movements and analysis, which can be applied for various diseases in a multicenter setting. METHODS: Development of a protocol to Demonstrate Eye Movement Networks with Saccades (DEMoNS) using infrared oculography. Automated analysis methods were used to calculate parameters describing the characteristics of the saccadic eye movements. The two measurements of the subjects were compared with descriptive and reproducibility statistics. RESULTS: Infrared oculography measurements of all subjects were performed using the DEMoNS protocol and various saccadic parameters were calculated automatically from 28 subjects. Saccadic parameters such as: peak velocity, latency and saccade pair ratios showed excellent reproducibility (intra-class correlation coefficients > 0.9). Parameters describing performance of more complex tasks showed moderate to good reproducibility (intra-class correlation coefficients 0.63-0.78). CONCLUSIONS: This study provides a standardized and transparent protocol for measuring and analyzing saccadic eye movements in a multicenter setting. The DEMoNS protocol details outcome measures for treatment trial which are of excellent reproducibility. The DEMoNS protocol can be applied to the study of saccadic eye movements in various neurodegenerative and motor diseases.

The temporal retinal vessel angle and infants born preterm.

AIM: To determine the temporal retinal vessel angle in babies and its relation to preterm birth. METHODS: Digital images were obtained during routine screening for retinopathy of prematurity (ROP). The temporal retinal vessel angle was measured in 164 eyes of 82 babies born "very preterm" (24-27 weeks gestational age (GA)), "preterm" (28-31 weeks GA), and "near term" (>/=32 weeks GA). RESULTS: Mean temporal vessel angle (TVA) for all three GA groups together is 80.0 degrees (SD 17.0 degrees ) for the right eye and 80.5 degrees (16.7 degrees ) for the left eye. The range is right eye 59-106 degrees , left eye 69-97 degrees , with 95% data above 67 degrees for the right and 63 degrees for the left eye. For babies born near term, TVA is 82 degrees in each eye. There is a high degree of interocular symmetry between right and left eyes and a statistically insignificant trend for increasing TVA with increasing GA. The presence and stage of ROP affected one parameter of the left eye alone. CONCLUSIONS: These data provide normative data on the TVA in babies and will facilitate, especially if there is interocular asymmetry, determining whether there is macular displacement.

The Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire: cultural adaptation and validation of the Greek version.

AIM: To adapt cross-culturally the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) for use in Greek patients with atrial fibrillation (AF) and to evaluate its psychometric properties. METHODS: Professional translators were involved in the inverse translation procedure. Twenty patients with AF participated in the cultural adaptation procedure. One hundred two consecutive patients participated in the validation process that included reliability (internal consistency, test-retest reliability) and validity assessment (face validity, construct validity). RESULTS: Greek AFEQT showed high internal consistency (Cronbach's alpha for overall scale: 0.97, subscales: Symptoms: 0.90, Daily Activities: 0.93, Treatment Concern: 0.91, Treatment Satisfaction: 0.83) and test-retest reliability (Spearman's rho: 0.99, p <0.001, Wilcoxon's test, p =0.959). Face validity was rated with a median of 7 by the patients. Finally, Greek AFEQT showed appropriate construct validity of demonstrating adequate convergent validity with the moderate to strong correlations of AFEQT domains with the Physical and Mental Component Summaries of SF-12 (Spearman's rho: 0.53-0.78, p <0.001). CONCLUSIONS: The Greek version of AFEQT has shown good psychometric properties and can be a useful tool in future studies on the quality of life of patients with AF. Hippokratia 2016, 20(4): 264-267.

Metabolic Adaptations of Plant Respiration to Nutritional Phosphate Deprivation.

Plants respond adaptively to orthophosphate (Pi) deprivation through the induction of alternative pathways of glycolysis and mitochondrial electron transport. These respiratory bypasses allow respiration to proceed in Pi-deficient plant cells because they negate the necessity for adenylates and Pi, both pools of which are severely depressed following nutritional Pi starvation.

The Fungicide Phosphonate Disrupts the Phosphate-Starvation Response in Brassica nigra Seedlings.

The development of Brassica nigra seedlings over 20 d of growth was disrupted by the fungicide phosphonate (Phi) in a manner inversely correlated with nutritional inorganic phosphate (Pi) levels. The growth of Pi-sufficient (1.25 mM Pi) seedlings was suppressed when 10, but not 5, mM Phi was added to the nutrient medium. In contrast, the fresh weights and root:shoot ratios of Pi-limited (0.15 mM) seedlings were significantly reduced at 1.5 mM Phi, and they progressively declined to about 40% of control values as medium Phi concentration was increased to 10 mM. Intracellular Pi levels generally decreased in Phi-treated seedlings, and Phi accumulated in leaves and roots to levels up to 6- and 16-fold that of Pi in Pi-sufficient and Pi-limited plants, respectively. Extractable activities of the Pi-starvation-inducible enzymes phosphoenolpyruvate phosphatase and inorganic pyrophosphate-dependent phosphofructokinase were unaltered in Pi-sufficient seedlings grown on 5 or 10 mM Phi. However, when Pi-limited seedlings were grown on 1.5 to 10 mM Phi (a) the induction of phosphoenolpyruvate phosphatase and inorganic pyrophosphate-dependent phosphofructokinase activities by Pi limitation was reduced by 40 to 90%, whereas (b) soluble protein concentrations and the activities of the ATP-dependent phosphofructokinase and pyruvate kinase were unaffacted. It is concluded that Phi specifically interrupts processes involved in regulation of the Pi-starvation response in B. nigra.