bluuebunny/crossref_metadata_2025 huggingface dataset:
OCCIPITAL NERVE BLOCK: AUDIT OF A DEVELOPING SERVICE
Authors: Wojtowicz Alex , Flower Michael , Hadjikoutis Savvas
Published: October 2015

Background

Occipital nerve block (ONB) is an injection of local anaesthetic, often with corticosteroid, given around the greater occipital nerve in primary and secondary headache disorders. Growing local demand and sparse national guidance prompted this audit to aid service design.

Aim

Establish local demand and efficacy of ONB. We will then consider changes to the service and re- audit.

Standards

No national guidelines available; standards determined through literature review.

Methods

Retrospective review of local ONBs for January–August 2014. Data reported by patients (n=17) through standardised questions, asking about each ONB administered (n=23).

Results

Patients experienced a mean 23 days headache freedom, 42% reduction in headache severity, and 38% reduction in headache days per week. Mean duration of effect was 44 days. Analgesia use fell after 70%, but 9% increased. Mild complications included injection site pain (65%); no moderate or severe complications.

Discussion

These data support the use of ONB to treat headache. Sample is insufficient to determine efficacy by headache type. The following targets are identified for improving the service; audit will be repeated following implementation:

1. Improve staffing and facilities for this increasingly popular service.

2. Formalise follow-up arrangements.

3. Consider routine scheduling of repeat procedures for appropriate patients.
TREATMENT OF NEUROLOGICAL MANIFESTATIONS OF SJOGREN'S SYNDROME
Authors: Dodd Katherine , Pegg Emily , Brown Rachael , Shaunak Sandip
Published: October 2015

Neurological manifestations of primary Sjogren's syndrome appear to be wide ranging. Treatment is recommended for those with progressive neurological impairment: usually immunosuppressive treatments including cyclophosphamide, steroids, azathioprine, and anti-TNF agents.

We present three cases that didn't respond to initial steroid treatment but subsequently improved with regular infusions of intravenous immunoglobulins. In all three cases, the initial anti–Ro test was negative, but became positive after 4–11 years, an important feature to recognise in clinical practice.

Case one presented with painful dystonic spasms of the arm and leg, hemi-facial spasm, vertigo, diplopia with skew deviation, and trigeminal neuropathy. Several years later she developed features of systemic mixed connective tissue disease. Case two presented as a facial palsy, sensory trigeminal neuropathy, and spastic quadraparesis. GAD antibody was positive but she did not clinically fit with stiff man syndrome. Case three has had relapsing inflammatory optic neuropathy since the age of 19, with no clear cause initially identified.

These cases highlight the diversity in the neurological manifestations of Sjogren's syndrome, the importance of not relying on initial antibody testing, and the potential for improvement with intravenous immunoglobulins, a treatment that has less adverse effects than potentially toxic immunosuppressants.
AUTOIMMUNE RETINOPATHY – IMPORTANCE OF RECOVERIN B ANTIBODIES
Authors: Sturrock Aaron , Karim Abid , Denniston Alastair , Jacob Saiju
Published: October 2015

Progressive visual failure can be secondary to autoimmune retinopathy (AIR). Presentation include progressive nyctalopia and peripheral field constriction. We present two patients with autoimmune retinopathy and their clinical progression.

A 70-year-old lady was referred to the neuroimmunology clinic with progressive nyctalopia and periorbital pain to exclude the possibility of an immune-mediated retinopathy. Visual acuity was 6/18 bilaterally with peripheral visual constriction. OCT showed disruption of the photoreceptor layers. A retinal antibody screen showed positive anti-Recoverin B antibodies. In view of the paraneoplastic association of this antibody, a thorough search for an underlying tumour was performed (CT, PET) and endobronchial ultrasound guided biopsy showed high grade neuro-endocrine small cell lung cancer. Oncological treatment coupled with IVIg therapy stabilised visual function for over 18 months at last follow-up.

A 47-year-old gentleman was referred with a three month history of bilateral visual decline and slightly altered personality. Retinal antibody screen showed cytoplasmic staining of inner nuclear layer. Extensive screening for an underlying neoplasia has been negative.

AIR can be cancer-associated (CAR), melanoma-associated (MAR) or non-paraneoplastic (nPAIR). Presence of Recoverin B antibodies should prompt thorough screening for underlying neoplasia. Treatment of cancer coupled with immunomodulatory therapy may help in halting progressive visual loss.
ANTI-VOLTAGE GATED POTASSIUM CHANNEL (VGKC) ANTIBODY POSITIVE ENCEPHALOPATHY
Authors: Kemp Michael , Kimber Jeff , Zhang Liqun
Published: October 2015

Since autoimmune mediated encephalitis was recognised 15 years ago, several autoantibodies have been identified. We present 3 patients with positive VGKC antibodies to emphasise the spectrum of clinic presentation and value of antibody testing.

A 61 yo male presented with cognitive decline and frequent right arm stiffening, which is recognised as faciobrachial dystonic seizure. VGKC/LGI1 antibody positive. Received IVIG treatment and rapidly recovered.

A 69 yo women presented with acute personality change and poor short memory following a brief syncope. MRI showed bilateral hippocampus high T2/FLAIR signal. VGKC/LGI-1 antibody was 5800. She improved with IVIG and steroid treatment. However, seizures recurred when weaning from steroid at 4 months. Repeat titre of 1100. Steroid restarted until antibody negative.

A 60 yo male presented with 8 months of personality change without myoclonus. VGKC antibody was positive with a titre of 169. Further testing LGI1 and CASPA2 were negative. He gradually recovered with 6 month steroid treatment. No specific cause was found with extensive investigations.

The typical presentations of VGKC encephalitis have been widely recognised, however clinical vigilance is important for atypical presentations. Antibody titres are of great value following the treatment, while low positive cases prompt further investigations.
MANAGEMENT OF SUSPECTED ENCEPHALITIS IN A UK TEACHING HOSPITAL
Authors: Binks Sophie , Cooper Rebecca , Wood Ruth , Martin Llewelyn
Published: October 2015

Introduction

Though infective encephalitis is relatively rare, prompt treatment significantly improves outcomes. In 2012, new national guidelines for management of suspected viral encephalitis were launched. We audited cases at Brighton and Sussex University Hospitals NHS Trust.

Method

Cases were identified retrospectively via medical coding and pharmacy records of patients to whom IV aciclovir was dispensed, between April 1 2012–June 30 2013. 42 cases were audited against the guidelines.

Results

In 10 cases (24%), the final diagnosis was encephalitis but in only one was an organism confirmed (varicella). Time to suspecting encephalitis ranged from on admission to 27 days. No LP was performed in seven cases, and achieved in <6 hours in four (10%). Paired plasma glucose was not performed in 51% of LPs. Almost all patients (95%) started aciclovir, and 76% received MRI brain at a median of 3 days. HIV testing was performed in 60%. 26% were admitted to ITU and 24% died.

Conclusions

Encephalitis is difficult to confirm and eventual differential of suspected cases is wide. The rate of ITU admission and death demonstrates the vulnerabilities of this cohort. While most patients received LP, aciclovir and MRI, there remains room for improvement in timing and completeness of investigations.
SPORADIC CREUTZFELDT-JAKOB DISEASE PRESENTING WITH A ‘JERKY ALIEN LIMB’
Authors: Vinjam Maruthi Ravi , Butterworth Steven , Davey Richard
Published: October 2015

A 64 yr old right-handed mechanic presented with four weeks history of clumsy right hand with ongoing problems at work. He described stiffness and problems with co-ordination. At the time of presentation he was noted to be walking with his right arm behind him and not being aware of this. His initial examination showed Mini Mental Score of 26/30, with ongoing involuntary movements of his right arm (Video).

Video shows spontaneous elevation of right arm with occasional myoclonic jerks. Video also demonstrates patient's difficulty in following simple motor tasks and his comments that his arm “has a mind of its own”.

His MRI head (Figure 1) showed typical cortical ribboning pattern described in sporadic CJD and CSF Protein for 14-3-3, s100b and RT-QUIC findings were consistent with the diagnosis of CJD.

Over next 4 weeks his cognitive function rapidly deteriorated with progressive worsening of his myoclonus. He died 4 weeks after his hospital discharge.

There are three broad varieties of alien limb phenomenon (ALP) types described in the literature, frontal, callosal and sensory. Jerky (myoclonic) ALP is well described in patients with CJD, so CJD should be in the differentials in any patient presenting with sub-acute onset of ALP.
LPS INDUCES AGGREGATION OF α-SYNUCLEIN IN MONOCYTES
Authors: Koopman Herjan , Jackson Simon , Anichtchik Oleg , Carroll Camille
Published: October 2015

It is well recognised that Parkinson's disease (PD) is associated with gastrointestinal problems appearing before onset of motor symptoms. An important role for the enteric nervous system (ENS) has been suggested. We hypothesize that inflammatory responses are involved in the onset and progression of PD, with a pivotal role for monocytes/macrophages in the gut. We show that lipopolysaccharide (LPS) can induce the expression and aggregation of monomeric α-synuclein in a human monocyte cell line (MM6). 24 Hours stimulation with LPS resulted in 3-6.5-fold increase in monomeric α-synuclein (determined by Western blotting), whilst tetrameric α-synuclein increased 1.3-2.2-fold. Preliminary results suggest that trimeric α-synuclein is secreted extracellularly after stimulation with LPS. Specificity of the observed bands was confirmed by pre-absorbing the antibody with recombinant α-synuclein. These findings were supported by immunocytochemistry: double immunofluorescence showed co-localization of aggregated α-synuclein with an antibody recognizing only oligomeric α-synuclein, confirming the presence of aggregates. These results suggest a role for inflammatory responses leading to increased monomeric and aggregated α-synuclein levels in monocytes. Secreted α-synuclein oligomers could mimic ‘prion-like’ spreading of aggregates to neurons, as observed in interneuronal transfer. The combination of aggregated α-synuclein with inflammatory mediators could influence the ENS, affecting onset and progression of PD.
iPAD-BASED ASSESSMENT IN PARKINSON'S DISEASE
Authors: Noad Rupert , Newman Craig , Carroll Camille , Zajicek John
Published: October 2015

Background

In order to facilitate neuroprotective trials in Parkinson's disease (PD), there is a need for improved means of early disease detection and measuring disease progression. Computerised assessment may afford easier and increasingly accurate administration of motor and cognitive tests, as well as measurement of indices not readily accessible with standard testing paradigms.

Aim

To develop and validate iPad-based cognitive and motor measures in PD.

Method

62 PD patients and 42 age-matched controls completed traditional and iPad versions of the Trail Making Test (TMT) (executive function) and Knox Cube Test (visual memory), as well as a range of other measures.

Results

Median age was 68 years; median MOCA score was 26. No participant had previously used an iPad. There was significant correlation between traditional and iPad measures: TMTa r=0.74, p<0.001; TMTb r=0.76, p<0.001; Knox r=0.63, p<0.001. Usability data were strong, 90% of participants providing positive feedback.

Conclusion

This initial study has demonstrated that two iPad-based measures of cognition are acceptable to PD patients and perform similarly to traditional pen-and-paper tests. Further work will extend the analysis of the measured indices in longitudinal studies to determine correlation with disease progression, and extend the battery of iPad-based tests available for PD assessment.
ECG ABNORMALITIES IN ALTERNATING HEMIPLEGIA: A BROADENED PHENOTYPE
Authors: Jaffer Fatima , Avbersek Andreja , IAHRC  , ENRAH  , Hanna Michael G , Houlden Henry , Kaski Juan P , Cross Helen , Sisodiya Sanjay M
Published: October 2015

Introduction

Alternating hemiplegia of Childhood (AH) caused by de novo mutations in ATP1A3, is characterised by recurrent plegic and dystonic episodes, seizures, non-paroxysmal neurological features, and dysautonomia. Premature mortality is observed and attributed to sudden unexpected death in epilepsy. A single case of asystole in AH is reported. Other neuronal channelopathies have cardiac involvement, and since ATP1A3 is expressed in cardiomyocytes, we hypothesised that ECG abnormalities are present in AH.

Methods

52 patients fulfilling the diagnostic criteria for AH were recruited, and screened for ATP1A3 mutations. ECGs were analysed for heart rate, cardiac axis, PR, QRS, RR, and QTc intervals, repolarisation patterns, and J-point abnormalities.

Results

53.8% exhibited abnormal resting 12-lead ECGs independent of seizures or AH episodes; 48.1% had repolarisation abnormalities. The proportion of intraventricular conduction delay or partial right bundle branch block was greater in this cohort compared to the general population. ECG abnormalities were significantly greater in patients >16 years than in those <16 years (p=0.0095), and also within the most common mutation group (D801N; p=0.045).

Conclusions

These ECG abnormalities reflect impaired repolarisation reserve in AH in an age-dependent manner, and may account for some cases of premature mortality observed. Long-term cardiac surveillance in AH is recommended.
CONSTIPATION PRECEDING PARKINSON'S DISEASE–META-ANALYSIS
Authors: Adams-Carr Kerala , Schrag Anette , Shribman Samuel , Bestwick Jonathan , Lees Andrew , Noyce Alastair
Published: October 2015

Constipation is a well-recognised non-motor feature of Parkinson's disease (PD) and has been reported to predate PD in a number of observational studies, in some cases by over two decades. A systematic review and meta-analysis was carried out following MOOSE criteria. The literature search was undertaken on 7 December 2014 using PubMed and the relevant search terms ‘Parkinson's disease’ and ‘Constipation’. Articles were screened for suitability and included if they met the specific criteria: observational studies with a cohort or case–control design; cases were patients with PD according to standard clinical criteria; controls were healthy or had no history of neurological disease; cohorts were representative of the general population; constipation in controls was assessed over the same time period as for patients; original data were reported. Data were extracted and combined using a fixed-effects model. Nine studies were included in the meta-analysis. Constipation was associated with an OR of 2.28 (95% confidence interval 2.10-2.46; p<0.001) for subsequent PD, offering further evidence that people with constipation are at a higher risk of developing PD and constipation may predate PD diagnosis by many years. This could have implications for our understanding of the pathogenesis of disease and planning of neuroprotective interventional trials.
DISCRIMINATION IN DYSTONIA: TIME FOR A RETHINK?
Authors: Sadnicka Anna , Daum Corinna , Manohar Sanjay , Rothwell John , Edwards Mark
Published: October 2015

Introduction

Abnormal temporal discrimination thresholds (TDT) are thought to reflect abnormal temporal processing in dystonia. Despite widespread use of the TDT paradigm the task has been developed little since its inception; even though current paradigms may test additional factors unrelated to temporal processing.

Method

22 healthy subjects and 22 subjects with cervical dystonia (CD) were tested with two novel tasks. The first task ‘gap detection’ was a forced choice version of the TDT. Complicating spatial elements of the paradigm were removed and modelling data psychophysically increased the dimensionality of analysis informing on task performance. The second task ‘interval discrimination’ tested the ability to classify the length of two successive intervals.

Results

Gap detection Equality of performance between groups was seen for general markers of performance such as hit rate, false positive rate and modelled psychometric function parameters. However, subjects with CD were significantly slower to make decisions. Interval discrimination No difference in the sensitivity between groups to classify differences in intervals was seen.

Conclusions

These results are surprising and challenge currently held concepts about the significance of previously documented abnormalities of TDTs in which a simple timing deficit is widely assumed. We hope that the ensuing discussion re-invigorates work to define the true biological correlate of TDT anomalies in dystonia as this will provide critical insight into its pathogenesis.
Mucosal immunity and upper respiratory tract symptoms in recreational endurance runners
Authors: Ihalainen Johanna K. , Schumann Moritz , Häkkinen Keijo , Mero Antti A.
Published: October 2015

The present study investigated the effects of a 12-week endurance-training intervention on salivary proteins and upper respiratory tract symptoms (URS) in 25 young men. Saliva samples of 25 recreational male endurance runners (age 34.6 years, body mass index = 23.8 kg·m−2, peak aerobic capacity = 47.2 mL·kg−1·min−1) were collected before (PRE) and after (POST) the training intervention, in a fasting state, as well as both before and after a maximal incremental treadmill run. The training consisted of both continuous and interval training sessions, 4–6 times per week based on the polarized training approach. Participants filled in Wisconsin Upper Respiratory Symptom Survey-21 and were retrospectively divided into 2 groups according to whether they reported URS (URS group, n = 13) or not (HEALTHY group, n = 12). Basal salivary immunoglobulin A (sa-sIgA) levels were significantly higher (+70%, p < 0.05) in the HEALTHY group both at PRE and POST whereas no significant differences were observed in salivary immunoglobulin M, salivary immunoglobulin G, lysozyme, or salivary α-amylase activity (sAA). Sa-sIgA concentration at PRE significantly correlated with the number of sick-days (R = –0.755, p < 0.001) in all subjects. The incremental treadmill run acutely increased sAA significantly (p < 0.05) at PRE (200%) and POST (166%) in the HEALTHY group but not in the URS group. This study demonstrated that subjects, who experienced URS during the 12 weeks of progressive endurance training intervention, had significantly lower basal sa-sIgA levels both before and after the experimental endurance training period. In addition to sa-sIgA, acute sAA response to exercise might be a possible determinant of susceptibility to URS in endurance runners.
MEETING THE NEEDS FOR MORE FISH THROUGH AQUACULTURE
Authors: GIAP D. H. , LAM T. J.
Published: October 2015

Fish is one of the major sources of animal protein. Due to rising world populations, increasing income and urbanization, demand for fish has been increasing. In order to meet the need for more fish, aquaculture has become increasingly important as wild populations and production from capture fisheries have declined due to overfishing and poor management. In recent years, production from aquaculture has increased rapidly to address the shortfalls in capture fisheries, especially in Asia where aquaculture production accounts for about 90% of world aquaculture production by volume. This paper reviews the status of the world’s fish production, provides an update on Asian aquaculture, and highlights developments that are contributing to sustainable fish production, particularly integrated multi-trophic aquaculture and aquaponics.
A MODERATION STUDY OF ORGANISATIONAL INTEGRATION AND NPD PROCESS PROFICIENCY IN THE U.S. AND KOREAN HEAVY CONSTRUCTION EQUIPMENT INDUSTRIES
Authors: MILLSON MURRAY R. , KIM JONGBAE
Published: October 2015

This study explores the potential differences between the relationships relating the market success of new products, the proficiency with which new product development (NPD) activities are executed during NPD processes, and the degree of organisational integration among various groups during NPD processes in the (U.S.) and Korea. This research addresses three major research questions: (1) Does NPD process proficiency impact new product market success in U.S. and Korean firms? (2) Does organisational integration impact new product market success in U.S. and Korean firms? and (3) Does country moderate the relationships between NPD process proficiency and new product market success, and between organisational integration and new product market success? This study is based on NPD data related to new product projects from the heavy construction equipment industries in the U.S. and Korea. Based on our combined model, it was found that NPD process development proficiency significantly impacts new product market success but organisational integration does not impact new product market success. Additionally, it was found that country moderates the NPD process proficiency-NPD market success and NPD organisational integration-NPD market success relationships. Study implications and recommendations are provided for NPD managers based on this research.
Influence of Moxifloxacin on Hepatic Redox Status and Plasma Biomarkers of Hepatotoxicity and Nephrotoxicity in Rat
Authors: Ore Ayokanmi , Olayinka Ebenezer Tunde
Published: October 2015

Moxifloxacin is a broad spectrum fluoroquinolone antibacterial agent. We examined the hepatic redox status and plasma biomarkers of nephrotoxicity and hepatotoxicity in rat following administration of moxifloxacin (MXF). Twenty-four Wistar rats, 180–200 g, were randomized into four groups (I–IV). Animals in group I (control) received 1 mL of distilled water, while animals in groups II, III, and IV received 1 mL each of MXF equivalent to 4 mg/kg b.w., 8 mg/kg b.w., and 16 mg/kg b.w., respectively. After seven days, plasma urea, bilirubin, and creatinine were significantly (P<0.05) elevated in the MXF-treated animals. Activities of alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase were significantly increased in the plasma of MXF-treated animals compared to control. Also plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides increased significantly in the MXF-treated groups relative to control. Moreover, MXF triggered a significant decrease in hepatic catalase, superoxide dismutase, and glutathione-Stransferase activities. Likewise, MXF caused a decrease in the hepatic levels of glutathione and vitamin C. A significant increase in hepatic MDA content was also observed in the MXF-treated animals relative to control. Overall, our data suggest that the half-therapeutic, therapeutic, and twice the therapeutic dose of MXF induced nephrotoxicity, hepatotoxicity, and altered hepatic redox balance in rats.
Bone Regeneration by Nanohydroxyapatite/Chitosan/Poly(lactide-co-glycolide) Scaffolds Seeded with Human Umbilical Cord Mesenchymal Stem Cells in the Calvarial Defects of the Nude Mice
Authors: Wang Fei , Su Xiao-Xia , Guo Yu-Cheng , Li Ang , Zhang Yin-Cheng , Zhou Hong , Qiao Hu , Guan Li-Min , Zou Min , Si Xin-Qin
Published: October 2015

In the preliminary study, we have found an excellent osteogenic property of nanohydroxyapatite/chitosan/poly(lactide-co-glycolide) (nHA/CS/PLGA) scaffolds seeded with human umbilical cord mesenchymal stem cells (hUCMSCs)in vitroand subcutaneously in the nude mice. The aim of this study was to further evaluate the osteogenic capacity of nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice. Totally 108 nude mice were included and divided into 6 groups: PLGA scaffolds + hUCMSCs; nHA/PLGA scaffolds + hUCMSCs; CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds without seeding; the control group (no scaffolds) (n=18). The scaffolds were implanted into the calvarial defects of nude mice. The amount of new bones was evaluated by fluorescence labeling, H&E staining, and Van Gieson staining at 4 and 8 weeks, respectively. The results demonstrated that the amount of new bones was significantly increased in the group of nHA/CS/PLGA scaffolds seeded with hUCMSCs (p<0.01). On the basis of previous studiesin vitroand in subcutaneous implantation of the nude mice, the results revealed that the nHA and CS also enhanced the bone regeneration by nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice at early stage.
Building Integrated Ontological Knowledge Structures with Efficient Approximation Algorithms
Authors: Xiang Yang , Janga Sarath Chandra
Published: October 2015

The integration of ontologies builds knowledge structures which brings new understanding on existing terminologies and their associations. With the steady increase in the number of ontologies, automatic integration of ontologies is preferable over manual solutions in many applications. However, available works on ontology integration are largely heuristic without guarantees on the quality of the integration results. In this work, we focus on the integration of ontologies with hierarchical structures. We identified optimal structures in this problem and proposed optimal and efficient approximation algorithms for integrating a pair of ontologies. Furthermore, we extend the basic problem to address the integration of a large number of ontologies, and correspondingly we proposed an efficient approximation algorithm for integrating multiple ontologies. The empirical study on both real ontologies and synthetic data demonstrates the effectiveness of our proposed approaches. In addition, the results of integration between gene ontology and National Drug File Reference Terminology suggest that our method provides a novel way to perform association studies between biomedical terms.
Moxibustion Reduces Ovarian Granulosa Cell Apoptosis Associated with Perimenopause in a Natural Aging Rat Model
Authors: Shi Xiao-Lan , Zhao Chen , Yang Shuai , Hu Xiao-Ying , Liu Shi-Min
Published: October 2015

In recent years, concerns about the adverse effects of hormone replacement therapy have increased interest in alternative therapies for the management of the symptoms of perimenopause. Here, we investigated the effects of moxibustion, a traditional Chinese practice that is involved in heated Artemisia vulgaris (mugwort) stimulation, on hormonal imbalance and ovarian granulosa cell (GC) apoptosis in a rat model of perimenopause. Our results showed that mild warm moxibustion (MWM) modulated the circulating levels of estradiol and follicle-stimulating hormone and their receptors and inhibited apoptosis in the ovaries of perimenopausal rats, similar to the effect of estrogen. Further investigation revealed that the effects of MWM on ovary tissues and cultured GCs were mediated by the modulation of the activity of Forkhead box protein O1 and involved the JAK2/STAT3 pathway. Our results provide information on the factors and pathways modulated by MWM and shed light on the mechanism underlying the beneficial effect of moxibustion on the symptoms of perimenopause.
Delirium Accompanied by Cholinergic Deficiency and Organ Failure in a 73-Year-Old Critically Ill Patient: Physostigmine as a Therapeutic Option
Authors: Zujalovic Benedikt , Barth Eberhard
Published: October 2015

Delirium is a common problem in ICU patients, resulting in prolonged ICU stay and increased mortality. A cholinergic deficiency in the central nervous system is supposed to be a relevant pathophysiologic process in delirium. Acetylcholine is a major transmitter of the parasympathetic nervous system influencing several organs (e.g., heart and kidneys) and the inflammatory response too. This perception might explain that delirium is not an individual symptom, but rather a part of a symptom complex with various disorders of the whole organism. The cholinergic deficiency could not be quantified up to now. Using the possibility of bedside determination of the acetylcholinesterase activity (AChE activity), we assumed to objectify the cholinergic homeostasis within minutes. As reported here, the postoperative delirium was accompanied by a massive hemodynamic and renal deterioration of unclear genesis. We identified the altered AChE activity as a plausible pathophysiological mechanism. The pharmacological intervention with the indirect parasympathomimetic physostigmine led to a quick and lasting improvement of the patient’s cognitive, hemodynamic, and renal status. In summary, severe delirium is not always an attendant phenomenon of critical illness. It might be causal for multiple organ deterioration if it is based on cholinergic deficiency and has to be treated at his pathophysiological roots whenever possible.
Optimizing Anti-EGFR Therapy in Colorectal Cancer
Authors: Salazar Ramon , Ciardiello Fortunato
Published: October 2015

Treatment with anti-EGFR monoclonal antibodies has been successfully integrated in the continuum of care for metastatic colorectal cancer. The major challenge is the identification of patients who would benefit from treatment. Currently, the best predictor of efficacy is the absence of mutations in KRAS and NRAS genes. Clin Cancer Res; 21(24); 5415–6. ©2015 AACR.

See related article by Peeters et al., p. 5469
Dapsone Therapy for Pustular Psoriasis: Case Series and Review of the Literature
Authors: Sheu Johanna S. , Divito Sherrie J. , Enamandram Monica , Merola Joseph F.
Published: October 2015

Background: Pustular psoriasis is an uncommon psoriasis variant, clinically characterized as small sterile pustules on an erythematous base. Evidence for therapy is lacking, and many currently employed systemic therapeutics carry risks of significant side effects, without specifically targeting disease etiology which includes the aggregation of neutrophils. Observations: We report therapy with the anti-neutrophil agent dapsone in 5 patients with pustular psoriasis and provide a brief review of the literature. Four patients responded to oral dapsone and 1 to topical dapsone therapy. All 5 patients had previously failed multiple topical and systemic treatments. In 2 cases, oral dapsone allowed for the discontinuation of other systemic agents. One patient stopped oral dapsone due to a side effect of sleep disturbance. Conclusion: Dapsone has a much safer side effect profile and may target the pathophysiology of pustular psoriasis more directly than many other systemic agents. As such, dapsone should be considered for the treatment of patients with pustular psoriasis.
Effect of Different Respiratory Modes on Return of Spontaneous Circulation in a Newborn Piglet Model of Hypoxic Cardiac Arrest
Authors: Mendler Marc R. , Weber Claudia , Hassan Mohammad A. , Huang Li , Waitz Markus , Mayer Benjamin , Hummler Helmut D.
Published: October 2015

Background: There are no clear evidence-based recommendations on the use of different techniques of respiratory support and chest compressions (CC) during neonatal cardiopulmonary resuscitation (CPR). Objectives: To determine the effects of different respiratory support strategies along with CC representing clinical practice on the return of spontaneous circulation (ROSC) in hypoxic newborn piglets with cardiac arrest. We hypothesized that use of a T-piece resuscitator (TPR) providing positive end-expiratory pressure (PEEP) reduces time to ROSC as compared to a self-inflating bag (SIB) without PEEP. Furthermore, we explored the effects of a ventilator providing inflations without synchrony to CC. Methods: Thirty-three newborn piglets were exposed to hypoxia until asystole occurred and randomized into three groups and resuscitated according to ILCOR guidelines: group 1 = TPR [peak inspiratory pressure (PIP)/PEEP of 25/5 cm H2O, rate 30/min], inflations interposed between CC (3:1 ratio); group 2 = SIB (PIP of 25 cm H2O without PEEP, rate 30/min), inflations interposed between CC (3:1 ratio), and group 3 = ventilator (PIP/PEEP of 25/5 cm H2O, rate 30/min), CC were applied with a rate of 120/min without synchrony to inflations. Animals were supported for 120 min after ROSC. Primary outcome was time to ROSC. Results: All animals achieved ROSC. We found no significant difference in time to ROSC between groups [median (IQR); TPR: 150 s (150-210); SIB: 150 s (120-180); ventilator: 180 s (150-345)]. There was no difference in use of epinephrine, in blood gases or hemodynamic parameters during the 120-min observation time after ROSC. Conclusions: We found no significant effect of different respiratory support strategies during CPR on ROSC.
Stereotype Threat Lowers Older Adults' Self-Reported Hearing Abilities
Authors: Barber Sarah J. , Lee Soohyoung Rain
Published: October 2015

Background: Although stereotype threat is a well-documented phenomenon, previous studies examining it in older adults have almost exclusively focused on objective cognitive outcomes. Considerably less attention has been paid to the impact of stereotype threat on older adults' subjective assessments of their own abilities or to the impact of stereotype threat in noncognitive domains. Objective: Older adults are stereotyped as having experienced not only cognitive declines, but physical declines as well. The current study tested the prediction that stereotype threat can negatively influence older adults' subjective hearing abilities. Methods: To test this, 115 adults (mean age 50.03 years, range 41-67) read either a positive or negative description about how aging affects hearing. All participants then answered a questionnaire in which they assessed their own hearing abilities. Results: The impact of stereotype threat on self-reported hearing was moderated by chronological age. Participants in their 40s and early 50s were unaffected by the stereotype threat manipulation. In contrast, participants in their late 50s and 60s rated their hearing as being subjectively worse when under stereotype threat. Conclusion: The current study provides a clear demonstration that stereotype threat negatively impacts older adults' subjective assessments of their own abilities. It is also the first study to demonstrate an effect of stereotype threat within the domain of hearing. These results have important implications for researchers investigating age-related hearing decline. Stereotype threat can lead to overestimation of the prevalence of age-related hearing decline. It can also serve as a confounding variable when examining the psychosocial correlates of hearing loss. Because of this, researchers studying age-related hearing loss should aim to provide a stereotype threat-free testing environment and also include assessments of stereotype threat within their studies.
ERG-Mediated Cell Invasion: A Link between Development and Tumorigenesis
Authors: Blee Alexandra M. , Huang Haojie
Published: October 2015

The transcription factor ERG is important during development for vasculogenesis and angiogenesis, blood vessel integrity, and maintenance of hematopoietic stem cells. In human adults, ERG is only expressed in endothelial cells and performs similar roles as in development to mediate blood vessel formation. However, aberrant overexpression of ERG in the adult contributes to diseases like prostate cancer, and the molecular and cellular mechanisms of ERG in tumorigenesis remain largely unclear. Studies of ERG-positive prostate cancers have shown that ERG promotes cell invasion and metastasis and contributes to poor patient prognosis. Together, these studies reveal ERG-mediated cell invasion as a potential link between normal ERG function in development and oncogenic ERG function in prostate cancer.
The Molecular Mechanism of Diastolic Heart Failure
Authors: Gu Jialin , Zhao Feiran , Wang Yuqi , Gao Junjie , Wang Xiaolong , Xue Jingui , Zhou Hua
Published: October 2015

Diastolic heart failure (DHF) is a group of clinical syndromes related to the performance of the pulmonary circulation and systemic circulation, with normal left ventricular (LV) systolic function. The pathophysiology of diastolic dysfunction includes delayed relaxation, impaired LV filling, and/or increased stiffness. These conditions result in impaired LV diastolic relaxation ability and a decrease in myocardial compliance. In recent years, studies on the mechanisms of DHF have focused on the renin-angiotensin-aldosterone system, inflammatory cytokines, oxidative stress, the process of myocardial calcium cycling, and associated proteins. The pathomechanism has been proven to be due to a deficiency in ATP, and Ca2+ cannot be reduced by sarcoplasmic reticulum calcium pump (SERCA2a), which leads to myocardial diastolic dysfunction. The correlation between the degradation process of ATP and its metabolites and DHF has also been studied in recent years. This paper summarizes the views on the above and analyzes the correlations between the molecular mechanisms.
The Impact of Familial Predisposition to Obesity and Cardiovascular Disease on Childhood Obesity
Authors: Nielsen Louise Aas , Nielsen Tenna Ruest Haarmark , Holm Jens-Christian
Published: October 2015

The prevalence of childhood obesity has reached alarming rates world-wide. The aetiology seems to be an interplay between genetic and environmental factors, and a surrogate measure of this complex interaction is suggested as familial predisposition. Familial predisposition to obesity and related cardiovascular disease (CVD) complications constitute the presence of obesity and/or obesity-related complications in primarily blood-related family members. The approaches of its measurement and applicability vary, and the evidence especially of its influence on obesity and obesity treatment in childhood is limited. Studies have linked a familial predisposition of obesity, CVD (hypertension, dyslipidaemia and thromboembolic events), and type 2 diabetes mellitus to BMI as well as other adiposity measures in children, suggesting degrees of familial aggregation of metabolic derangements. A pattern of predispositions arising from mothers, parents or grandparents as being most influential have been found, but further comprehensive studies are needed in order to specify the exact implications of familial predisposition. In the scope of childhood obesity this article reviews the current literature regarding familial predisposition to obesity and obesity-related complications, and how these familial predispositions may impact obesity in the offspring.
Speculative Propositions: A Visual Pattern Sampler
Authors: Syjuco Stephanie
Published: October 2015

During World War I, a peculiar example of disruptive patterning was developed to adorn British and American battleships. “Dazzle camouflage” as it was known, did little to “hide” the vessels themselves. Rather, its function was to confuse enemy aim by utilizing chaotic black-and-white patterns. Vintage photographs of these ships provide startling visuals of a kind of graphical warfare. At first glance, the extreme angles and cutout shapes conjure everything from European Modernist abstraction, Russian Constructivism, and colonial ethnic and tribal patterning, to later forms of Op art and design. As an artist researching these images, I began speculating on the side-effects of their routes as global visual transmitters of conquest and empire. What if these patterns, likened to war paint and symbolic markers of dominance, were altered to show their transmission onto other forms, such as modern architecture, commodities, and trade/transit routes—a sort of cross-pollination of hybridity and influence across cultures and continents? How can these patterns be employed by unexpected “clients” of economic and cultural colonialism? How can colonized forms misappropriate this visual technique for themselves? Speculative Propositions: A Visual Pattern Sampler is the result of this exploration.
Turning Digitised Newspapers into Networks of Political Elites
Authors: Hicks Jacqueline , Traag Vincent A. , Reinanda Ridho
Published: October 2015

This paper introduces the Elite Network Shifts (ENS) project to the Asian Studies community where computational techniques are used with digitised newspaper articles to describe changes in relations among Indonesian political elites. Reflecting on how “political elites” and “political relations” are understood by the elites, as well as across the disciplinary boundaries of the social and computational sciences, it suggests ways to operationalise these concepts for digital research. It then presents the results of a field trip where six Indonesian political elites were asked to evaluate the accuracy of their own computational networks generated by the project. The main findings of the paper are: (1) The computational identification of political elites is relatively successful, while much work remains on categorising their relations, (2) social scientists should focus on capturing single dimensions of complex social phenomena when using computational techniques, and (3) computational techniques are not able to capture multiple understandings of social concepts.
Quantifying dominance of adult female white-tailed deer in the presence of abundant food
Authors: Michel Eric S. , Demarais Stephen , Strickland Bronson K. , Belant Jerrold L. , Millspaugh Joshua J.
Published: October 2015

Dominance is a behavioural mechanism that allows individuals to access and monopolize resources which should ultimately improve their fitness. Hierarchy strength should be strongest when resources are limited; however, this relationship is not consistent. We provided abundant food to assess whether hierarchy strength was consistent with resource abundance using 9 groups of captive female white-tailed deer (Odocoileus virginianus). We further assessed how body mass, age and testosterone levels were associated with rank position. Deer displayed a weak hierarchy with a mean linearity () of 0.39 (SD = 0.09) and a mean directional consistency index of 0.83 (SD = 0.06). Rank was related to body mass (, slope = 0.011), but not age or testosterone levels (). We demonstrate that hierarchy strength was weak in the presence of abundant food resources and suggest the possibility that dominance is a plastic behaviour that may vary with resource abundance.
The Crossed Destinies or Two Philosophers: Louis Althusser and Merab Mamardashvili
Authors: Epelboin Annie
Published: October 2015

The Sorbonne professor, who knew Mamardashvili personally, gives a biographical insight into the Georgian philosopher’s relationship with Louis Althusser, the leading French Left-wing theoretician. She does this on the basis of the correspondence between the two philosophers which lasted as long as their friendship. It began shortly after their first meeting in Paris in 1966 and ended in 1980, when Althusser was committed to a psychiatric hospital following the murder of his wife. The letters were at first sent very officially by post and addressed to the respective places of work, to Althusser at the École Normal Supérieure rue Ulm and to Mamardashvili at the Institute of the Workers Movement in Moscow. Later they were carried by messengers, including the author of the article.
Thought in Culture
Authors: Mamardashvili Merab K.
Published: October 2015

This essay on “Thought in Culture” was published twice in Russian, in 1989 and 1990, both versions being transcriptions of Mamardashvili’s lectures delivered orally. This English translation, by the Dutch philosophical scholar, Evert van der Zweerde, is the first to be published. The question of thought is considered in the context of the question of suicide, albeit not in the sense Albert Camus spoke of it, but, in the sense of the old philosophers, as the existence of the primordial evil in human nature. This primordial evil is in Man’s powerlessness (немогота), in that which is beyond Man’s capacity. Through this dialectic of power and powerlessness, Mamardashvili explores the relationship of the structure and function of thought in culture.
A Moment in Mamardashvili’s Conception of Non-Classical Rationality
Authors: Regnier Daniel
Published: October 2015

In the article the author examines a reference made by Merab Mamardashvili in his book Classical and Non-classical Ideals of Rationality to the work of the Georgian psychologist Dimitri Uznadze (1886–1950). Uznadze’s concepts are introduced and described for the purpose of establishing how Uznadze’s overall project as represented by his theory of “set” can lead to a better understanding of certain basic intentions of Mamardashvili’s philosophy. This is done primarily through an analysis of Mamardashvili’s reception of Uznadze’s theory of set.
Husserl’s Cartisian Meditations and Mamardashvili’s Cartesian Reflections
Authors: Motroshilova Nelly
Published: October 2015

Mamardashvili thought and wrote about Descartes and Proust, but at the same time he wrote about himself – about his “duell of honour” with the hidden world of secrets, about the state of “one on one” before the harshness of existence, about his own search for twice lost (because violently divided) time, about the at first glance unsuccessful attempts to check the affair of his life’s “race with death” (his works appeared only posthumously). The Russian academician, Nelly Motroshilova, weaves an intricate analytic of Mamardashvili’s relationship with phenomenological thought in general and Husserl’s philosophy in particular, in the context of rich biographical details.
The dorsal chaetotaxy of first instar Trogolaphysa jataca, with description of twelve new species of Neotropical Trogolaphysa (Hexapoda: Collembola: Paronellidae)
Authors: SOTO-ADAMES FELIPE N.
Published: October 2015

Adult members of tribe Paronellini are characterized by a substantially reduced idiochaetotaxy and as a result chaeta homology determination is often ambiguous. To evaluate previous hypotheses of chaetae homology in adult Trogolaphysa, a complete description of the dorsal chaetotaxy of first instar Trogolaphysa jataca (Wray, 1953b), supplemented with observations on first instar Trogolaphysa paracarpenteri sp. nov., is presented. It is showed that first instar Trogolaphysa carries an almost complete set of dorsal chaetae and that the reduction in adult idiochaetotaxy is secondary. In addition, the organization of primary chaetae in T. jataca points to a closer relationship with genera in subfamily Entomobryinae than to Orchesellinae. Based on chaetae correspondence between first instar and adult T. jataca it is established that the inner median chaetae on adult head corresponds to M1 instead of S1, the mesothorax p3 complex includes chaetae p1-p4, and on the fourth abdominal segment, anterior macrochaeta on column A corresponds to A3, and the secondary bothriotrix corresponds to D3p. In addition, T. relicta (Palacios-Vargas, Ojeda & Christiansen, 1985) is re-described based on a paratype, and 12 new species are described: from Mexico, T. stannardi sp. nov., T. dimorphica sp. nov., T. laterolineata sp. nov., T. marieloiseae sp. nov., T. clarencei sp. nov., T. ocellata sp. nov., T. paracarpenteri sp. nov., T. palaciosi sp. nov., T. octosetosa sp. nov., and T. trioculata sp. nov.; from Jamaica, T. balteata sp. nov.; and from Argentina, T. entreriosensis sp. nov.