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Aims Capgras syndrome is the most common of the delusional misidentification syndromes. It is characterised by the delusional belief that a familiar person has been replaced by an identical imposter. Capgras syndrome is associated with functional conditions, like psychosis, but also with a range of organic conditions such as dementia, brain injury and Parkinson's disease. The COVID-19 pandemic created a unique situation where patients were unable to see their relatives in person, resulting in their only form of contact being via telephone or virtually. Methods We present a case of a 70 year old lady Mrs W, who was admitted with first episode psychosis. She developed Capgras syndrome during her admission, based purely in the auditory modality of talking to her husband on the telephone. She was firm in her conviction that he was an imposter, mainly based of ‘a different tone’ and using ‘different words’. Showing a photograph of her husband was met with full and appropriate recognition. Given that a significant minority of elderly patients with a Capgras delusion have an organic aetiology, neuroimaging and extended laboratory investigations, including auto-antibodies for limbic encephalitis, were performed which were unremarkable. With psychotropic medication, the Capgras delusion resolved, and on discharge she recognised her husband when they met again. Results The aetiology of Capgras syndrome remains unclear, although a range of causes have been suggested. Early psychodynamic theories related to conflict between love and hate towards the relative, which could be relevant in functional conditions but may have less significance in organic conditions. Other theories examine Capgras syndrome as a mirror of prosopagnosia, where people have difficulties recognising familiar faces. This would indicate a pathological process affecting visual pathways. However, our case challenges this theory, suggesting that deficits in other sensory modality pathways may also contribute. Although rare, our case is not entirely unique; several cases of Capgras syndrome in people with blindness have been reported. However, our case differs in that our patient was able to recognise photos of her husband despite misidentification based on auditory cues. As Mrs W did not have visual impairment, it is unclear if she would have presented with the more classical visual misidentification in the absence of the unique circumstances of the COVID-19 pandemic. Conclusion Capgras syndrome is classically associated with misidentification based on visual cues, however a growing number of case reports challenge this. Further investigation is required to create theories that encompass other sensory modalities.

The objective of this study is to highlight the superannuation industry in Australia as an exemplar and then compare this to other countries. To this end, an overview of the literature in the field considers various countries and their approaches. What emerges is that profound inequities in retirement funding will continue unless policies change. Superannuation tends to work well for males who are employed full time but less well for females in general and other groups such as the long-term unemployed, self-employed, contractors, transient populations, indigenous and people with illness and addictions. Having entire cohorts of citizens cascade into poverty upon retirement is a political embarrassment and a human rights issue. This is effectively a wicked problem that can be addressed by well-designed proactive social marketing and redesigned government and industry policy. Governments and industry should work together to find a way to augment the retirement plans of females and other marginalized groups.

Abstract Background There are more than 18 million cancer survivors in the United States. Yet, survivors of color remain under-represented in cancer survivorship research (Saltzman et al. in Contemp Clin Trials Commun 29:100986, 2022; Pang et al. in J Clin Oncol 34:3992–3999, 2016; Lythgoe et al. in Prostate Cancer Prostatic Dis 24:1208–1211, 2021). Our long-term goal is to enroll and follow a cohort of historically under-represented cancer survivors, to better understand modifiable risk factors that influence clinical and quality of life outcomes in these populations. Towards that goal, we describe herein how we applied community-based participatory research approaches to develop inclusive study materials for enrolling such a cohort. Methods We implemented community engagement strategies to inform and enhance the study website and recruitment materials for this cohort including: hiring a dedicated engagement coordinator/community health educator as a member of our team; working with the Helen Diller Family Comprehensive Cancer Center Office of Community Engagement (OCE) and Community Advisory Board members; presenting our educational, research, and study recruitment materials at community events; and establishing a community advisory group specifically for the study (4 individuals). In parallel with these efforts, 20 semi-structured user testing interviews were conducted with diverse cancer survivors to inform the look, feel, and usability of the study website. Results Engagement with community members was a powerful and important approach for this study’s development. Feedback was solicited and used to inform decisions regarding the study name (eat move sleep, EMOVES), logo, study website content and imagery, and recruitment materials. Based on community feedback, we developed additional educational materials on healthy groceries and portion size in multiple languages and created a study video. Conclusions Including an engagement coordinator as a permanent team member, partnering with the institutional community outreach and engagement resources (i.e., OCE), and allocating dedicated time and financial support for cultivating relationships with stakeholders outside the university were critical to the development of the study website and materials. Our community guided strategies will be tested as we conduct enrollment through community advisor networks and via the state cancer registry.

The function of a specific tissue and its biomechanics are interdependent, with pathologies or ageing often being intertwined with structural decline. The biomechanics of Caenorhabditis elegans, a model organism widely used in pharmacological and ageing research, has been established as biomarker for healthy ageing. However, the properties of the constituent tissues, and their contribution to the overall mechanical characteristics of the organism, remain relatively unknown. In this study we investigated the biomechanics of healthy C. elegans cuticle, muscle tissue, and pseudocoelom using a combination of indentation experiments and in silico modelling. We performed stiffness measurements using an atomic force microscope. To approximate the nematode’s cylindrical body we used a novel three-compartment nonlinear finite element model, enabling us to analyse of how changes in the elasticity of individual compartments affect the bulk stiffness. We then fine-tuned the parameters of the model to match the simulation force-indentation output to the experimental data. To test the finite element model, we modified distinct compartments experimentally. Our in silico results, in agreement with previous studies, suggest that hyperosmotic shock reduces stiffness by decreasing the internal pressure. Unexpectedly, treatment with the neuromuscular agent aldicarb, traditionally associated with muscle contraction, reduced stiffness by decreasing the internal pressure. Furthermore, our finite element model can offer insights into how drugs, mutations, or processes such as ageing target individual tissues.

Purpose – This study is an attempt to apply the techniques of semiotics in conjunction with quantitative analysis to decode and interpret an advertisement which promotes the South Australian Barossa Valley as a tourist destination. Design/methodology/approach – A survey was submitted to a Southeast Asian student and postgraduate sample. Regression analysis and qualitative analysis were carried out, which suggested that the advertisement was engaging the majority of the audience. Findings – Most respondents expressed a desire to visit the location and used language which was evocative and connective. Those who did not or who were turned off by the advertisement's content expressed themselves in language which terminated further engagement. Research limitations/implications – The sample was a non-target group, but this is an advantage because it provides a base level of unconditioned response. Practical implications – A better understanding of semiotics may reinforce other areas of marketing endeavour such as social marketing approaches which are gaining more importance in the still developing COVID-19 economy. This methodology can be extended to other marketing communication contexts. Social implications – Once campaigns have been aimed at target audiences, there may be potential to orientate another campaign at non-target audiences using the same advertisement. In terms of global marketing, this is extension rather than adaptation. Originality/value – This study provides an example of how marketing could use semiotics in conjunction with quantitative methods to determine an audience's response and the intention to purchase a product or service.

Background: Black/African Americans are receiving COVID-19 vaccines at much lower rates than whites. However, research is still evolving that explains why these vaccination rates are lower. The aim of this study was to examine the effects of the pandemic among older Black/African Americans, with an emphasis on trust and vaccine intention prior to vaccine development. Methods: Data were collected between July and September 2020 from 8 virtual focus groups in Detroit, MI and San Francisco Bay Area, CA with 33 older African Americans and 11 caregivers of older African Americans with cognitive impairment, supplemented by one virtual meeting with the project's Community Advisory Board. Inductive/deductive content analysis was used to identify themes. Results: Five major themes influenced the intention to be vaccinated: uncertainty, systemic abandonment, decrease in trust, resistance to vaccines, and opportunities for vaccination. The last theme, opportunities for vaccination, emerged as a result of interaction with our CAB while collecting project data after the vaccines were available which provided additional insights about potential opportunities that would promote the uptake of COVID-19 vaccination among older Black/African Americans. The results also include application of the themes to a multi-layer framework for understanding precarity and the development of an Integrated Logic Model for a Public Health Crisis. Conclusions: These findings suggest that trust and culturally relevant information need to be addressed immediately to accelerate vaccine uptake among older Black/African Americans. New initiatives are needed to foster trust and address systemic abandonment from all institutions. In addition, culturally relevant public health campaigns about vaccine uptake are needed. Thus, systemic issues need immediate attention to reduce health disparities associated with COVID-19.

Annually, an estimated seven million deaths are linked to exposure to airborne pollutants. Despite extensive epidemiological evidence supporting clear associations between poor air quality and a range of short- and long-term health effects, there are considerable gaps in our understanding of the specific mechanisms by which pollutant exposure induces adverse biological responses at the cellular and tissue levels. The development of more complex, predictive, in vitro respiratory models, including two- and three-dimensional cell cultures, spheroids, organoids and tissue cultures, along with more realistic aerosol exposure systems, offers new opportunities to investigate the cytotoxic effects of airborne particulates under controlled laboratory conditions. Parallel advances in high-resolution microscopy have resulted in a range of in vitro imaging tools capable of visualizing and analysing biological systems across unprecedented scales of length, time and complexity. This article considers state-of-the-art in vitro respiratory models and aerosol exposure systems and how they can be interrogated using high-resolution microscopy techniques to investigate cell–pollutant interactions, from the uptake and trafficking of particles to structural and functional modification of subcellular organelles and cells. These data can provide a mechanistic basis from which to advance our understanding of the health effects of airborne particulate pollution and develop improved mitigation measures.

Summary: The ability of tumors to establish a pro-tumorigenic microenvironment is an important point of investigation in the search for new therapeutics. Tumors form microenvironments in part by the “education” of immune cells attracted via chemotactic axes such as that of CCR5-CCL5. Further, CCR5 upregulation by cancer cells, coupled with its association with pro-tumorigenic features such as drug resistance and metastasis, has suggested CCR5 as a therapeutic target. However, with several conformational “pools” being reported, phenotypic investigations must be capable of unveiling conformational heterogeneity. Addressing this challenge, we performed super-resolution structured illumination microscopy (SIM) and single molecule partially TIRF-coupled HILO (PaTCH) microscopy of CCR5 in fixed cells. SIM data revealed a non-random spatial distribution of CCR5 assemblies, while Intensity-tracking of CCR5 assemblies from PaTCH images indicated dimeric sub-units independent of CCL5 perturbation. These biophysical methods can provide important insights into the structure and function of onco-immunogenic receptors and many other biomolecules.

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a check point protein expressed on the surface of T cells and plays a central role in regulating the immune response. In recent years, CTLA-4 has become a popular target for cancer immunotherapy in which blocking CTLA-4 can restore T-cell function and enhance the immune response against cancer. Currently, there are many CTLA-4 inhibitors in a variety of modalities, including cell therapies, which are being developed in both preclinical and clinical stages to further harness the potential of the target for the treatment of certain types of cancer. In drug discovery research, measuring the level of CTLA-4 in T cells is important for drug discovery and development because it provides key information for quantitative assessment of the pharmacodynamics, efficacy, and safety of the CTLA-4-based therapies. However, to our best knowledge, there is still no report of a sensitive, specific, accurate, and reliable assay for CTLA-4 measurement. In this work, an LC/MS-based method was developed to measure CTLA-4 in human T cells. The assay demonstrated high specificity with an LLOQ of 5 copies of CTLA-4 per cell when using 2.5 million T cells for analysis. As shown in the work, the assay was successfully used to measure CTLA-4 levels in subtype T-cell samples from individual healthy subjects. The assay could be applied in supporting the studies of CTLA-4-based cancer therapies.

Abstract Background Contemporary perioperative fasting guidelines aim to alleviate patient discomfort before surgery and enhance postoperative recovery whilst seeking to reduce the risk of pulmonary aspiration during anesthesia. The impact of a short message service (SMS) reminder on fasting guideline compliance is unknown. Therefore, we performed a retrospective observational study and quality improvement project aiming to quantify the extent of excessive and prolonged fasting, and then assessed the impact of a SMS reminder in reducing fasting times. Methods After ethics committee approval we performed a retrospective observational study investigating preoperative fasting times of adult patients undergoing elective surgery. First, we assessed whether the fasting guideline times were adhered to (Standard Care group). All patients received internationally recommended fasting guidelines in the form of a written hospital policy document. We then implemented an additional prompt via a mobile phone SMS 1 day prior to surgery containing a reminder of fasting guideline times (SMS group). The primary aims were to compare fasting times between the Standard Care group and the SMS group. Results The fasting times of 160 patients in the Standard Care group and 110 patients in the SMS group were evaluated. Adherence to the fasting guidelines for solids occurred in 14 patients (8.8%) in the Standard Care group vs. Twenty-two patients (13.6%) in the SMS group (p=0.01). Adherence to the fasting guidelines for fluids occurred in 4 patients (2.5%) in the Standard Care group vs. Ten patients (6.3%) in the SMS group (p=0.023). Patients in the Standard Care group had a longer median (inter-quartile range (IQR)) fasting time for fluids compared the SMS group [6.5 h (IQR 4.5:11) vs 3.5 h (IQR 3:8.5), p

Abstract Background Progressive cerebellar ataxia is a neurodegenerative disorder without effective treatment options that seriously hinders quality of life. Previously, transcranial direct current stimulation (tDCS) has been demonstrated to benefit cerebellar functions (including improved motor control, learning and emotional processing) in healthy individuals and patients with neurological disorders. While tDCS is an emerging therapy, multiple daily sessions are needed for optimal clinical benefit. This case study tests the symptomatic benefit of remotely supervised tDCS (RS-tDCS) for a patient with cerebellar ataxia. Methods We report a case of a 71-year-old female patient with progressive cerebellar ataxia, who presented with unsteady gait and balance impairment, treated with tDCS. tDCS was administered using our RS-tDCS protocol and was completed daily in the patient’s home (Monday – Friday) with the help of a trained study technician. tDCS was paired with 20 min of simultaneous cognitive training, followed by 20 min of physical exercises directed by a physical therapist. Stimulation consisted of 20 min of 2.5 mA direct current targeting the cerebellum via an anodal electrode and a cathodal electrode placed over the right shoulder. The patient completed baseline and treatment end visits with neurological, cognitive, and motor (Lafayette Grooved Pegboard Test, 25 ft walk test and Timed Up and Go Test) assessments. Results The patient successfully completed sixty tDCS sessions, 59 of which were administered remotely at the patient’s home with the use of real time supervision as enabled by video conferencing. Mild improvement was observed in the patient’s gait with a 7% improvement in walking speed, which she completed without a walking-aid at treatment end, which was in stark contrast to her baseline assessment. Improvements were also achieved in manual dexterity, with an increase in pegboard scores bilaterally compared to baseline. Conclusions Results from this case report suggest that consecutively administered tDCS treatments paired with cognitive and physical exercise hold promise for improving balance, gait, and manual dexterity in patients with progressive ataxia. Remotely supervised tDCS provides home access to enable the administration over an extended period. Further controlled study in a large group of those with cerebellar ataxia is needed to replicate these findings. Trial registration ClinicalTrials.gov Identifier: NCT03049969. Registered 10 February 2017- Retrospectively registered.

Abstract Background Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has been shown to improve common symptoms of neurological disorders like depressed mood, fatigue, motor deficits and cognitive dysfunction. tDCS requires daily treatment sessions in order to be effective. We developed a remotely supervised tDCS (RS-tDCS) protocol for participants with multiple sclerosis (MS) to increase accessibility of tDCS, reducing clinician, patient, and caregiver burden. The goal of this protocol is to facilitate home use for larger trials with extended treatment periods. In this study we determine the generalizability of RS-tDCS paired with cognitive training (CT) by testing its feasibility in participants with Parkinson’s disease (PD). Methods Following the methods in our MS protocol development, we enrolled sixteen participants (n = 12 male, n = 4 female; mean age 66 years) with PD to complete ten open-label sessions of RS-tDCS paired with CT (2.0 mA × 20 min) at home under the remote supervision of a trained study technician. Tolerability data were collected before, during, and after each individual session. Baseline and follow-up measures included symptom inventories (fatigue and sleep) and cognitive assessments. Results RS-tDCS was feasible and tolerable for patients with PD, with at-home access leading to high protocol compliance. Side effects were mostly limited to mild sensations of transient itching and burning under the electrode sites. Similar to prior finding sin MS, we found preliminary efficacy for improvement of fatigue and cognitive processing speed in PD. Conclusions RS-tDCS paired with CT is feasible for participants with PD to receive at home treatment. Signals of benefit for reduced fatigue and improved cognitive processing speed are consistent across the PD and MS samples. RS-tDCS can be generalized to provide tDCS to a range of patients with neurologic disorders for at-home rehabilitation. Trial registration ClinicalTrials.gov Identifier: NCT02746705. Registered April 21st 2016.

Behavioural phenotyping of model organisms is widely used to investigate fundamental aspects of organism biology, from the functioning of the nervous system to the effects of genetic mutations, as well as for screening new drug compounds. However, our capacity to observe and quantify the full range and complexity of behavioural responses is limited by the inability of conventional microscopy techniques to capture volumetric image information at sufficient speed. In this article we describe how combining light field microscopy with computational depth estimation provides a new method for fast, quantitative assessment of 3D posture and movement of the model organism Caenorhabditis elegans (C. elegans). We apply this technique to compare the behaviour of cuticle collagen mutants, finding significant differences in 3D posture and locomotion. We demonstrate the ability of quantitative light field microscopy to provide new fundamental insights into C. elegans locomotion by analysing the 3D postural modes of a freely swimming worm. Finally, we consider relative merits of the method and its broader application for phenotypic imaging of other organisms and for other volumetric bioimaging applications.

During 2001–2014, predominant influenza A(H1N1) and A(H3N2) strains in South America predominated in all or most subsequent influenza seasons in Central and North America. Predominant A(H1N1) and A(H3N2) strains in North America predominated in most subsequent seasons in Central and South America. Sharing data between these subregions may improve influenza season preparedness.

Background and aims Accurate sizing of polyps at time of colonoscopy is critical for determining surveillance intervals. Endoscopists routinely over- or underestimate the size of polyps at colonoscopy. We evaluated the variability in sizing of polyps among multiple endoscopists, and the effect of patient and physician related factors on polyp size estimation in a large community-based practice. Methods Adult patients who underwent a colonoscopy with polypectomy at five endoscopy centers in Minneapolis/St. Paul by one of 52 endoscopists in 2013 were included in this study. Association of patient, physician, and procedure related factors on polyp sizing was assessed. Results In the study time frame, 38 624 colonoscopies were performed at five ambulatory endoscopy centers. Of these, 16 336 had one or more polyp removed with size information available, and were included in this analysis. There was significant inter-physician variation for estimating polyp sizes larger than 5 mm (intraclass correlation coefficient [ICC] 0.13). Older patient age (OR 1.08, 95 %CI 1.06 – 1.11), and male physician gender (OR 1.92, 95 %CI 1.26 – 2.94) were associated with increased odds of physicians sizing polyps as larger in size. Surveillance procedures had a higher odds of larger polyp sizing compared to screening (OR 0.91, 95 %CI 0.86 – 0.97) and diagnostic procedures (OR 0.86, 95 %CI 0.78 – 0.94). Conclusion In a large community setting, variation of polyp sizing estimates exists between physicians. Male physicians were more likely to size polyps as larger in size. Older patients and patients undergoing surveillance procedures were more likely to have polyps that were sized as larger in size.

Introduction: More than 200,000 midurethral slings are placed yearly for stress urinary incontinence. Approximately 14% to 20% of women experience worsening sexual function overall after these procedures. We postulated that sling placement injures neural pathways regulating “female prostate” tissue within the anterior vaginal wall. Aim: To perform a meta-analysis for overall sexual function and orgasm using validated questionnaires for transvaginal tape, transobturator tape, and their variants. Methods: Effect sizes of preoperative and postoperative questionnaire scores for overall sexual function and orgasm were calculated. Random-effects models were selected for meta-analyses. Statistical analysis involved determination of the ratio of total heterogeneity to total variability. Main Outcome Measures: Differences of overall sexual and orgasm functions were calculated by subtracting postoperative sling scores from preoperative sling scores. Forest plots of effect sizes were performed. Results: Sixty-seven percent of midurethral sling procedures analyzed showed no change or improvement in overall sexual function postoperatively, whereas 33% of studies analyzed for orgasm function showed improvement after the procedure. For transvaginal tape, mean total sexual function and orgasm postoperative scores were significantly higher than preoperative scores. For transobturator tape, mean total postoperative score was significantly higher than the preoperative score; however, the mean orgasm postoperative score was not significantly higher than the preoperative score, possibly because of variability in transobturator tape data. Conclusion: There is a discrepancy between postoperative sexual satisfaction and orgasmic function after midurethral sling surgery. Although overall sexual function remained the same or improved for most women, orgasmic function in only one third of cases improved overall, with most women experiencing no change or deterioration in orgasmic function. Dissection for, and placement of, the midurethral sling can compromise the neural integrity of the anterior vaginal wall, thereby detrimentally affecting the periurethral prostate tissue that is essential to the orgasmic response. We propose that this surgical procedure can compromise orgasmic function in some women. Szell N, Komisaruk B, Goldstein SW, et al. A Meta-Analysis Detailing Overall Sexual Function and Orgasmic Function in Women Undergoing Midurethral Sling Surgery for Stress Incontinence. Sex Med 2017;5:e84–e93.

Introduction: Optical techniques are routinely used to size and count extracellular vesicles (EV). For comparison of data from different methods and laboratories, suitable calibrators are essential. A suitable calibrator must have a refractive index (RI) as close to that of EV as possible but the RI of EV is currently unknown. To measure EV, RI requires accurate knowledge of size and light scattering. These are difficult to measure as most EVs cannot be resolved by light microscopy and their diameter is smaller than the wavelength of visible light. However, nanoparticle tracking analysis (NTA) provides both size and relative light scattering intensity (rLSI) values. We therefore sought to determine whether it was possible to use NTA to measure the RI of individual EVs. Methods: NTA was used to measure the rLSI and size of polystyrene and silica microspheres of known size and RI (1.470 and 1.633, respectively) and of EV isolated from a wide range of cells. We developed software, based on Mie scattering code, to calculate particle RI from the rLSI data. This modelled theoretical scattering intensities for polystyrene and silica microspheres of known size (100 and 200 nm) and RI. The model was verified using data from the polystyrene and silica microspheres. Size and rLSI data for each vesicle were processed by the software to generate RI values. Results: The following modal RI measurements were obtained: fresh urinary EV 1.374, lyophilised urinary EV 1.367, neuroblastoma EV 1.393, blood EV 1.398, EV from activated platelets 1.390, small placental EV 1.364–1.375 and 1.398–1.414 for large placental EV (>200 nm). Large placental EV had a significantly higher RI than small placental EV (p1.40 were observed for some large (>200 nm) microvesicles. Conclusion: This method for measuring EV RI will be useful for developing appropriate calibrators for EV measurement.

The seasonality of influenza in the tropics complicates vaccination timing. We investigated influenza seasonality in northern India and found influenza positivity peaked in Srinagar (34.09°N) in January–March but peaked in New Delhi (28.66°N) in July–September. Srinagar should consider influenza vaccination in October–November, but New Delhi should vaccinate in May–June.

Neuraminidase inhibitors are the only licensed antiviral medications available to treat avian influenza A(H7N9) virus infections in humans. According to a neuraminidase inhibition assay, an R292K substitution reduced antiviral efficacy of inhibitors, especially oseltamivir, and decreased viral fitness in cell culture. Monitoring emergence of R292K-carrying viruses using a pH-modified neuraminidase inhibition assay should be considered.

The white paper reports the deliberations of a workshop focused on biotic challenges to plant health held in Washington, D.C. in September 2016. Ensuring health of food plants is critical to maintaining the quality and productivity of crops and for sustenance of the rapidly growing human population. There is a close linkage between food security and societal stability; however, global food security is threatened by the vulnerability of our agricultural systems to numerous pests, pathogens, weeds, and environmental stresses. These threats are aggravated by climate change, the globalization of agriculture, and an over-reliance on nonsustainable inputs. New analytical and computational technologies are providing unprecedented resolution at a variety of molecular, cellular, organismal, and population scales for crop plants as well as pathogens, pests, beneficial microbes, and weeds. It is now possible to both characterize useful or deleterious variation as well as precisely manipulate it. Data-driven, informed decisions based on knowledge of the variation of biotic challenges and of natural and synthetic variation in crop plants will enable deployment of durable interventions throughout the world. These should be integral, dynamic components of agricultural strategies for sustainable agriculture.

In July 2004, an outbreak of influenza A (H3N2) was detected at 3 Bhutanese refugee camps in southeastern Nepal. Hemagglutination inhibition showed that ≈40% of the viruses from this outbreak were antigenically distinct from the A/Wyoming/3/03 vaccine strain. Four amino acid differences were observed in most of the 26 isolates compared with the A/Wyoming/3/2003 vaccine strain. All 4 substitutions are located within or adjacent to known antibody-binding sites. Several isolates showed a lysine-to-asparagine substitution at position 145 (K145N) in the hemagglutinin molecule, which may be noteworthy since position 145 is located within a glycosylation site and adjacent to an antibody-binding site. H3N2 viruses continue to drift from the vaccine strain and may remain as the dominant strains during the 2005–2006 influenza season. Thus, the 2005–2006 Northern Hemisphere vaccine strain was changed to A/California/7/2004, a virus with all 4 amino acid substitutions observed in these Nepalese isolates.

Objective. We examined the cause of transfer delay in patients with an acute ST-segment myocardial infarction (STEMI) from non percutaneous coronary intervention (PCI) capable to PCI capable hospitals. We then implemented a novel, simple, and reliable initiative to improve the transfer process. Background. Guidelines established by the ACC/AHA call for door-to-balloon times of ≤90 minutes for patients with STEMI. When hospital transfer is necessary, this is only met in 8.6% of cases. Methods. All patients presenting with STEMI to a non-PCI capable hospital from April 2006 to February 2009 were analyzed retrospectively. After identifying causes of transfer delay the “Register and Roll” initiative was developed. An analysis of effect was conducted from March 2009 to July 2011. Results. 144 patients were included, 74 pre-initiative and 70 post- initiative. Time to EMS activation was a major delay in patient transfer. After implementation, the EMS activation time has significantly decreased and time to reperfusion approaches recommended goal (Median 114 min versus 90 min, ), with 55% in

Polymerization into amyloid fibrils is a crucial step in the pathogenesis of neurodegenerative syndromes. Amyloid assembly is governed by properties of the sequence backbone and specific side-chain interactions, since fibrils from unrelated sequences possess similar structures and morphologies. Therefore, characterization of the structural determinants driving amyloid aggregation is of fundamental importance. We investigated the forces involved in the amyloid assembly of a model peptide derived from the oligomerization domain of acetylcholinesterase (AChE), AChE(586-599), through the effect of single point mutations on beta-sheet propensity, conformation, fibrilization, surfactant activity, oligomerization and fibril morphology. AChE(586-599) was chosen due to its fibrilization tractability and AChE involvement in Alzheimer's disease. The results revealed how specific regions and residues can control AChE(586-599) assembly. Hydrophobic and/or aromatic residues were crucial for maintaining a high beta-strand propensity, for the conformational transition to beta-sheet, and for the first stage of aggregation. We also demonstrated that positively charged side-chains might be involved in electrostatic interactions, which could control the transition to beta-sheet, the oligomerization and assembly stability. Further interactions were also found to participate in the assembly. We showed that some residues were important for AChE(586-599) surfactant activity and that amyloid assembly might preferentially occur at an air-water interface. Consistently with the experimental observations and assembly models for other amyloid systems, we propose a model for AChE(586-599) assembly in which a steric-zipper formed through specific interactions (hydrophobic, electrostatic, cation-pi, SH-aromatic, metal chelation and polar-polar) would maintain the beta-sheets together. We also propose that the stacking between the strands in the beta-sheets along the fiber axis could be stabilized through pi-pi interactions and metal chelation. The dissection of the specific molecular recognition driving AChE(586-599) amyloid assembly has provided further knowledge on such poorly understood and complicated process, which could be applied to protein folding and the targeting of amyloid diseases.

Neurodegenerative diseases associated with abnormal protein folding and ordered aggregation require an initial trigger which may be infectious, inherited, post-inflammatory or idiopathic. Proteolytic cleavage to generate vulnerable precursors, such as amyloid-beta peptide (Abeta) production via beta and gamma secretases in Alzheimer's Disease (AD), is one such trigger, but the proteolytic removal of these fragments is also aetiologically important. The levels of Abeta in the central nervous system are regulated by several catabolic proteases, including insulysin (IDE) and neprilysin (NEP). The known association of human acetylcholinesterase (hAChE) with pathological aggregates in AD together with its ability to increase Abeta fibrilization prompted us to search for proteolytic triggers that could enhance this process. The hAChE C-terminal domain (T40, AChE(575-614)) is an exposed amphiphilic alpha-helix involved in enzyme oligomerisation, but it also contains a conformational switch region (CSR) with high propensity for conversion to non-native (hidden) beta-strand, a property associated with amyloidogenicity. A synthetic peptide (AChE(586-599)) encompassing the CSR region shares homology with Abeta and forms beta-sheet amyloid fibrils. We investigated the influence of IDE and NEP proteolysis on the formation and degradation of relevant hAChE beta-sheet species. By combining reverse-phase HPLC and mass spectrometry, we established that the enzyme digestion profiles on T40 versus AChE(586-599), or versus Abeta, differed. Moreover, IDE digestion of T40 triggered the conformational switch from alpha- to beta-structures, resulting in surfactant CSR species that self-assembled into amyloid fibril precursors (oligomers). Crucially, these CSR species significantly increased Abeta fibril formation both by seeding the energetically unfavorable formation of amyloid nuclei and by enhancing the rate of amyloid elongation. Hence, these results may offer an explanation for observations that implicate hAChE in the extent of Abeta deposition in the brain. Furthermore, this process of heterologous amyloid seeding by a proteolytic fragment from another protein may represent a previously underestimated pathological trigger, implying that the abundance of the major amyloidogenic species (Abeta in AD, for example) may not be the only important factor in neurodegeneration.

Observed speech and interactive behavior of American Hmong students who were attending a northern California high school indicate that Hmong student responses to teacher generated questions were often influenced by culturally based predispositions. In answering certain types of content related questions, these students relied on underlying cultural emphases (pervasive culture specific themes) which were sometimes different from those generally held by Anglo American students and teachers at this school. Because of these differences, Hmong students often provided answers considered "wrong" in academic contexts, although they were essentially correct from a normative Hmong perspective. Moreover, Laotian Hmong students, often described as "shy" by educators, were found to be carrying out normative cultural rules for demonstrating respect and deference to authority figures through silence. This "taciturn style" was evident during numerous open ended question/answer sessions as these exchanges occurred in classroom situations. Constructing answers on the basis of Hmong cultural agendas and remaining silent in classroom situations produced impediments to communication between these students and their teachers. Moreover, many teachers often did not recognize these problems as the result of fundamental cultural differences.