Anatomical Comparative Study of the External Nasal Nerve in Caucasian and Asian:Application for Minimizing Nerve Damage in Rhinoplasty

BACKGROUND: The numbness of the nasal tip is the main symptom of the external nasal nerve injury, especially after rhinoplasty. This postoperative syndrome can reduce the patient’s satisfaction with the operation. Having a better understanding of the anatomical structure and intraoperative protection can effectively avoid nerve injury. At present, the anatomical research on this nerve is all from Asia. This study aims to fill the gap in the anatomical study of this nerve in Caucasians and provides comparative results with Asians. MATERIAL AND METHODS: A total of 20 Caucasian cadavers were embalmed using the Thiel method. On dissection, after complete exposure of the external nasal nerves, the distance between the exit point of the external nasal nerve and the nasal midline was measured, and the morphology of the nerves was compared with the Asian data. The nerves were classified into types based on their branching pattern. RESULTS: The nerve plane was the same as the Asian record. The distance ranged from 5.08 to 11.94 mm (mean, 8.31 ± 1.85 mm). This distance has statistical significant difference compared with the Asian population (P < 0.01). The average distance is larger, and the distribution range of the exit point is wider. On classification, 35 of 40 cases had the same type results as those previously reported, with the primary types I, II and III. Five new varieties were found which are classified as subtypes of the primary types and a new type IV. Furthermore, the bifurcation position in two-thirds of the type II cases and variations is proximal to that seen in the Asian population. CONCLUSIONS: The anatomical structure of the external nasal nerve in Caucasians and Asians has obvious differences. This nerve in Caucasians is more likely to be damaged during rhinoplasty than Asians. Except the primary types, the classification of the external nasal nerve also includes subtypes and type IV. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266

Brain amyloid in preclinical Alzheimer\u27s disease is associated with increased driving risk

INTRODUCTION: Postmortem studies suggest that fibrillar brain amyloid places people at higher risk for hazardous driving in the preclinical stage of Alzheimer's disease (AD). METHODS: We administered driving questionnaires to 104 older drivers (19 AD, 24 mild cognitive impairment, and 61 cognitive normal) who had a recent (18)F-florbetapir positron emission tomography scan. We examined associations of amyloid standardized uptake value ratios with driving behaviors: traffic violations or accidents in the past 3 years. RESULTS: The frequency of violations or accidents was curvilinear with respect to standardized uptake value ratios, peaking around a value of 1.1 (model r(2) = 0.10, P = .002); moreover, this relationship was evident for the cognitively normal participants. DISCUSSION: We found that driving risk is strongly related to accumulating amyloid on positron emission tomography, and that this trend is evident in the preclinical stage of AD. Brain amyloid burden may in part explain the increased crash risk reported in older adults

Predictors of return to driving after stroke

OBJECTIVE: While returning to driving is a major concern for many stroke survivors, predicting who will return to driving after a stroke is often difficult for rehabilitation professionals. The primary aim of this study was to identify patient factors present at admission to an inpatient rehabilitation hospital that can be used to identify which patients with acute stroke will and will not return to driving. DESIGN: After comparing returners and non-returners on demographic and clinical characteristics, a logistic regression model with return to driving as the outcome variable was built using the backward stepwise method. RESULTS: Thirty-one percent (48/156) of patients who had been driving before their stroke had returned to driving six months post-stroke. The final regression model, using FIM cognition and lower extremity Motricity Index scores, predicted the driving outcome with an accuracy of 75% (107/143). CONCLUSIONS: Patients with lower FIM cognition and lower extremity Motricity Index scores at admission to inpatient rehabilitation are less likely to return to driving at six months. This model could be used by rehabilitation professionals to help counsel patients and their families and focus treatment goals

Using the A/T/N framework to examine driving in preclinical Alzheimer’s disease

The A/T/N classification system is the foundation of the 2018 NIA-AA Research Framework and is intended to guide the Alzheimer disease (AD) research agenda for the next 5&ndash;10 years. Driving is a widespread functional activity that may be particularly useful in investigation of functional changes in pathological AD before onset of cognitive symptoms. We examined driving in preclinical AD using the A/T/N framework and found that the onset of driving difficulties is most associated with abnormality of both amyloid and tau pathology, rather than amyloid alone. These results have implications for participant selection into clinical trials and for the application time of interventions aimed at prolonging the time of safe driving among older adults with preclinical AD

Functional conservation of Pax6 regulatory elements in humans and mice demonstrated with a novel transgenic reporter mouse

<p>Abstract</p> <p>Background</p> <p>The Pax6 transcription factor is expressed during development in the eyes and in specific CNS regions, where it is essential for normal cell proliferation and differentiation. Mice lacking one or both copies of the <it>Pax6 </it>gene model closely humans with loss-of-function mutations in the <it>PAX6 </it>locus. The sequence of the Pax6/PAX6 protein is identical in mice and humans and previous studies have shown <it>structural </it>conservation of the gene's regulatory regions.</p> <p>Results</p> <p>We generated a transgenic mouse expressing green fluorescent protein (GFP) and neomycin resistance under the control of the entire complement of human <it>PAX6 </it>regulatory elements using a modified yeast artificial chromosome (YAC). Expression of GFP was studied in embryos from 9.5 days on and was confined to cells known to express Pax6. GFP expression was sufficiently strong that expressing cells could be distinguished from non-expressing cells using flow cytometry.</p> <p>Conclusion</p> <p>This work demonstrates the <it>functional </it>conservation of the regulatory elements controlling <it>Pax6/PAX6 </it>expression in mice and humans. The transgene provides an excellent tool for studying the functions of different <it>Pax6/PAX6 </it>regulatory elements in controlling Pax6 expression in animals that are otherwise normal. It will allow the analysis and isolation of cells in which <it>Pax6 </it>is activated, irrespective of the status of the endogenous locus.</p

Creating a driving profile for older adults using GPS devices and naturalistic driving methodology

Background/Objectives: Road tests and driving simulators are most commonly used in research studies and clinical evaluations of older drivers. Our objective was to describe the process and associated challenges in adapting an existing, commercial, off-the-shelf (COTS), in-vehicle device for naturalistic, longitudinal research to better understand daily driving behavior in older drivers. Design: The Azuga G2 Tracking DeviceTM was installed in each participant’s vehicle, and we collected data over 5 months (speed, latitude/longitude) every 30-seconds when the vehicle was driven.  Setting: The Knight Alzheimer’s Disease Research Center at Washington University School of Medicine. Participants: Five individuals enrolled in a larger, longitudinal study assessing preclinical Alzheimer disease and driving performance.  Participants were aged 65+ years and had normal cognition. Measurements:  Spatial components included Primary Location(s), Driving Areas, Mean Centers and Unique Destinations.  Temporal components included number of trips taken during different times of the day.  Behavioral components included number of hard braking, speeding and sudden acceleration events. Methods:  Individual 30-second observations, each comprising one breadcrumb, and trip-level data were collected and analyzed in R and ArcGIS.  Results: Primary locations were confirmed to be 100% accurate when compared to known addresses.  Based on the locations of the breadcrumbs, we were able to successfully identify frequently visited locations and general travel patterns.  Based on the reported time from the breadcrumbs, we could assess number of trips driven in daylight vs. night.  Data on additional events while driving allowed us to compute the number of adverse driving alerts over the course of the 5-month period. Conclusions: Compared to cameras and highly instrumented vehicle in other naturalistic studies, the compact COTS device was quickly installed and transmitted high volumes of data. Driving Profiles for older adults can be created and compared month-to-month or year-to-year, allowing researchers to identify changes in driving patterns that are unavailable in controlled conditions

Reconstituted B cell receptor signaling reveals carbohydrate-dependent mode of activation

Activation of immune cells (but not B cells) with lectins is widely known. We used the structurally defined interaction between influenza hemagglutinin (HA) and its cell surface receptor sialic acid (SA) to identify a B cell receptor (BCR) activation modality that proceeded through non-cognate interactions with antigen. Using a new approach to reconstitute antigen-receptor interactions in a human reporter B cell line, we found that sequence-defined BCRs from the human germline repertoire could be triggered by both complementarity to influenza HA and a separate mode of signaling that relied on multivalent ligation of BCR sialyl-oligosaccharide. The latter suggested a new mechanism for priming naïve B cell responses and manifested as the induction of SA-dependent pan-activation by peripheral blood B cells. BCR crosslinking in the absence of complementarity is a superantigen effect induced by some microbial products to subvert production of antigen-specific immune responses. B cell superantigen activity through affinity for BCR carbohydrate is discussed

Human Lipoxygenase Pathway Gene Variation and Association with Markers of Subclinical Atherosclerosis in the Diabetes Heart Study

Aims. Genes of the 5-lipoxygenase pathway are compelling candidates for atherosclerosis. We hypothesize that polymorphisms in ALOX12, ALOX15, ALOX5, and ALOX5AP genes are associated with subclinical atherosclerosis in multiple vascular beds. Methods. Families with two or more siblings with type 2 diabetes and their nondiabetic siblings were studied as part of the Diabetes Heart Study (DHS). European American diabetic (n = 828) and nondiabetic (n = 170) siblings were genotyped for SNPs in the ALOX12, ALOX15, ALOX5, and ALOX5AP genes. Subclinical measures of atherosclerosis (IMT, coronary (CorCP), carotid (CarCP) and aortic (AorCP) calcified plaque) were obtained. Results. Associations were observed between ALOX12 with CorCP, ALOX5 with CorCP, AorCP, and IMT, and ALOX5AP with CorCP and CarCP, independent of known epidemiologic risk factors. Further, lipoxygenase pathway SNPs that were associated with measures of atherosclerosis were associated with markers of inflammation (CRP, ICAM-1) and calcification (MGP). Conclusions. Polymorphisms within ALOX12, ALOX5, and ALOX5AP are genetically associated with subclinical atherosclerosis and with biomarkers of disease in families with type 2 diabetes. These results suggest that variants in lipoxygenase pathway genes may have pleiotropic effects on multiple components that determine risk of cardiovascular disease

Climate Services Can Support African Farmers' Context-Specific Adaptation Needs at Scale

We consider the question of what is needed for climate services to support sub-Saharan African farmers' adaptation needs at the scale of the climate challenge. Consistent with an earlier assessment that mutually reinforcing supply-side and demand-side capacity constraints impede the development of effective climate services in Africa, our discussion of strategies for scaling up practices that meet farmers' needs, and opportunities to address long-standing obstacles, is organized around: (a) meeting farmers' climate information needs; (b) supporting access, understanding and use; and (c) co-production of services. A widespread gap between available information and farmers' needs is associated with entrenched seasonal forecast convention and obstacles to using observational data. Scalable innovations for producing more locally relevant historical and forecast climate information for farm decision-making are beginning to be adopted. Structured participatory communication processes help farmers relate complex climate information to their experience, and integrate it into their management decisions. Promising efforts to deliver rural climate services strategically combine communication channels that include participatory processes embedded in existing agricultural advisory systems, and innovations in interactive broadcast media. Efforts to engage farmers in co-production of climate services improve delivery to farmers and dialogue among stakeholders, but often with little impact on the usability of available information. We discuss challenges and options for capturing farmers' evolving demands, and aggregating and incorporating this information into iterative improvements to climate services at a national scale. We find evidence that key weaknesses in the supply and the demand sides of climate services continue to reinforce each other to impede progress toward meeting farmers' needs at scale across Africa. Six recommendations target these weaknesses: (1) change the way seasonal forecasts are produced and presented regionally and nationally, (2) use merged gridded data as a foundation for national climate information products, (3) remove barriers to using historical data as a public good, (4) mobilize those who work on the demand side of climate services as an effective community of practice, (5) collectively assess and improve tools and processes for communicating climate information with rural communities, and (6) build iterative co-production processes into national climate service frameworks

Controlled overexpression of Pax6 in vivo negatively autoregulates the Pax6 locus, causing cell-autonomous defects of late cortical progenitor proliferation with little effect on cortical arealization

Levels of expression of the transcription factor Pax6 vary throughout corticogenesis in a rostro-lateral(high) to caudo-medial(low) gradient across the cortical proliferative zone. Previous loss-of-function studies have indicated that Pax6 is required for normal cortical progenitor proliferation, neuronal differentiation, cortical lamination and cortical arealization, but whether and how its level of expression affects its function is unclear. We studied the developing cortex of PAX77 YAC transgenic mice carrying several copies of the human PAX6 locus with its full complement of regulatory regions. We found that PAX77 embryos express Pax6 in a normal spatial pattern, with levels up to three times higher than wild type. By crossing PAX77 mice with a new YAC transgenic line that reports Pax6 expression (DTy54), we showed that increased expression is limited by negative autoregulation. Increased expression reduces proliferation of late cortical progenitors specifically, and analysis of PAX77↔wild-type chimeras indicates that the defect is cell autonomous. We analyzed cortical arealization in PAX77 mice and found that, whereas the loss of Pax6 shifts caudal cortical areas rostrally, Pax6 overexpression at levels predicted to shift rostral areas caudally has very little effect. These findings indicate that Pax6 levels are stabilized by autoregulation, that the proliferation of cortical progenitors is sensitive to altered Pax6 levels and that cortical arealization is not