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BackgroundOutbreaks of infectious diseases pose great risks, including hospitalization and death, to public health. Therefore, improving the management of outbreaks is important for preventing widespread infection and mitigating associated risks. Mobile health technology provides new capabilities that can help better capture, monitor, and manage infectious diseases, including the ability to quickly identify potential outbreaks. ObjectiveThis study aims to develop a new infectious disease surveillance (IDS) system comprising a mobile app for accurate data capturing and dashboard for better health care planning and decision making. MethodsWe developed the IDS system using a 2-pronged approach: a literature review on available and similar disease surveillance systems to understand the fundamental requirements and face-to-face interviews to collect specific user requirements from the local public health unit team at the Nepean Hospital, Nepean Blue Mountains Local Health District, New South Wales, Australia. ResultsWe identified 3 fundamental requirements when designing an electronic IDS system, which are the ability to capture and report outbreak data accurately, completely, and in a timely fashion. We then developed our IDS system based on the workflow, scope, and specific requirements of the public health unit team. We also produced detailed design and requirement guidelines. In our system, the outbreak data are captured and sent from anywhere using a mobile device or a desktop PC (web interface). The data are processed using a client-server architecture and, therefore, can be analyzed in real time. Our dashboard is designed to provide a daily, weekly, monthly, and historical summary of outbreak information, which can be potentially used to develop a future intervention plan. Specific information about certain outbreaks can also be visualized interactively to understand the unique characteristics of emerging infectious diseases. ConclusionsWe demonstrated the design and development of our IDS system. We suggest that the use of a mobile app and dashboard will simplify the overall data collection, reporting, and analysis processes, thereby improving the public health responses and providing accurate registration of outbreak information. Accurate data reporting and collection are a major step forward in creating a better intervention plan for future outbreaks of infectious diseases.

The fluorescent glutamate indicator iGluSnFR enables imaging of neurotransmission with genetic and molecular specificity. However, existing iGluSnFR variants exhibit low in vivo signal-to-noise ratios, saturating activation kinetics and exclusion from postsynaptic densities. Using a multiassay screen in bacteria, soluble protein and cultured neurons, we generated variants with improved signal-to-noise ratios and kinetics. We developed surface display constructs that improve iGluSnFR's nanoscopic localization to postsynapses. The resulting indicator iGluSnFR3 exhibits rapid nonsaturating activation kinetics and reports synaptic glutamate release with decreased saturation and increased specificity versus extrasynaptic signals in cultured neurons. Simultaneous imaging and electrophysiology at individual boutons in mouse visual cortex showed that iGluSnFR3 transients report single action potentials with high specificity. In vibrissal sensory cortex layer 4, we used iGluSnFR3 to characterize distinct patterns of touch-evoked feedforward input from thalamocortical boutons and both feedforward and recurrent input onto L4 cortical neuron dendritic spines.

Calcium imaging with protein-based indicators1,2 is widely used to follow neural activity in intact nervous systems, but current protein sensors report neural activity at timescales much slower than electrical signalling and are limited by trade-offs between sensitivity and kinetics. Here we used large-scale screening and structure-guided mutagenesis to develop and optimize several fast and sensitive GCaMP-type indicators3-8. The resulting 'jGCaMP8' sensors, based on the calcium-binding protein calmodulin and a fragment of endothelial nitric oxide synthase, have ultra-fast kinetics (half-rise times of 2 ms) and the highest sensitivity for neural activity reported for a protein-based calcium sensor. jGCaMP8 sensors will allow tracking of large populations of neurons on timescales relevant to neural computation.

Human trafficking continues to persist, affecting up to 200 million people worldwide. As clinicians in emergency departments commonly encounter victims of intimate partner violence, some of these encounters will be with trafficking victims. These encounters provide a rare opportunity for healthcare providers to intervene and help. This case report of a human trafficking patient from a teaching hospital illustrates the complexity in identifying these victims. Clinicians can better identify potential trafficking cases by increasing their awareness of this phenomenon, using qualified interpreters, isolating potential victims by providing privacy and using simple clear reassuring statements ensuring security. A multidisciplinary approach can then be mobilized to help these patients. [West J Emerg Med. 2010;11(5); 402-404.]

BACKGROUND: Identification of clinically significant genetic alterations involved in human disease has been dramatically accelerated by developments in next-generation sequencing technologies. However, the infrastructure and accessible comprehensive curation tools necessary for analyzing an individual patient genome and interpreting genetic variants to inform healthcare management have been lacking. RESULTS: Here we present the ClinGen Variant Curation Interface (VCI), a global open-source variant classification platform for supporting the application of evidence criteria and classification of variants based on the ACMG/AMP variant classification guidelines. The VCI is among a suite of tools developed by the NIH-funded Clinical Genome Resource (ClinGen) Consortium and supports an FDA-recognized human variant curation process. Essential to this is the ability to enable collaboration and peer review across ClinGen Expert Panels supporting users in comprehensively identifying, annotating, and sharing relevant evidence while making variant pathogenicity assertions. To facilitate evidence-based improvements in human variant classification, the VCI is publicly available to the genomics community. Navigation workflows support users providing guidance to comprehensively apply the ACMG/AMP evidence criteria and document provenance for asserting variant classifications. CONCLUSIONS: The VCI offers a central platform for clinical variant classification that fills a gap in the learning healthcare system, facilitates widespread adoption of standards for clinical curation, and is available at https://curation.clinicalgenome.org.

Maximizing the personal, public, research, and clinical value of genomic information will require the reliable exchange of genetic variation data. We report here the Variation Representation Specification (VRS, pronounced "verse"), an extensible framework for the computable representation of variation that complements contemporary human-readable and flat file standards for genomic variation representation. VRS provides semantically precise representations of variation and leverages this design to enable federated identification of biomolecular variation with globally consistent and unique computed identifiers. The VRS framework includes a terminology and information model, machine-readable schema, data sharing conventions, and a reference implementation, each of which is intended to be broadly useful and freely available for community use. VRS was developed by a partnership among national information resource providers, public initiatives, and diagnostic testing laboratories under the auspices of the Global Alliance for Genomics and Health (GA4GH).

Introduction: Bilingual aphasia is an atypical stroke presentation in the multilingual patient where an isolated aphasia occurs in one language while the other remains unaffected.Case Report: A multilingual male presented to the emergency department with expressive aphasia to English but who was still able to speak fluently in French. Receptive English was preserved. While his National Institute of Health Stroke Scale score was technically zero, his pure aphasia component qualified him as an exception. He regained some repetitive English, so fibrinolyitic therapy was not initiated.Conclusion: Bilingual aphasia is an indication for fibrinolysis given the impact that a pure aphasic stroke has on quality of life.

Femtosecond lasers at fixed wavelengths above 1,000 nm are powerful, stable and inexpensive, making them promising sources for two-photon microscopy. Biosensors optimized for these wavelengths are needed for both next-generation microscopes and affordable turn-key systems. Here we report jYCaMP1, a yellow variant of the calcium indicator jGCaMP7 that outperforms its parent in mice and flies at excitation wavelengths above 1,000 nm and enables improved two-color calcium imaging with red fluorescent protein-based indicators.

Introduction: Posttraumatic stress disorder (PTSD) is a mental health disorder caused by experiencing or witnessing traumatic events. Recent studies show that patients with PTSD have an increased risk of developing dementia, including Alzheimer's disease (AD), but there is currently no way to predict which patients will go on to develop AD. The objective of this study was to identify structural and functional neural changes in patients with PTSD that may contribute to the future development of AD. Methods: Neuroimaging (pseudo-continuous arterial spin labeling [pCASL] and structural magnetic resonance imaging [MRI]) and behavioral data for the current study (n = 67) were taken from our non-randomized open label clinical trial (ClinicalTrials.gov Identifier: NCT03229915) for treatment-seeking individuals with PTSD (n = 40) and age-matched healthy controls (HC; n = 27). Only the baseline measures were utilized for this study. Mean cerebral blood flow (CBF) and gray matter (GM) volume were compared between groups. Additionally, we utilized two previously established machine learning-based algorithms, one representing AD-like brain activity (Machine learning-based AD Designation [MAD]) and the other focused on AD-like brain structural changes (AD-like Brain Structure [ABS]). MAD scores were calculated from pCASL data and ABS scores were calculated from structural T1-MRI images. Correlations between neuroimaging data (regional CBF, GM volume, MAD scores, ABS scores) and PTSD symptom severity scores measured by the clinician-administered PTSD scale for DSM-5 (CAPS-5) were assessed. Results: Decreased CBF was observed in two brain regions (left caudate/striatum and left inferior parietal lobule/middle temporal lobe) in the PTSD group, compared to the HC group. Decreased GM volume was also observed in the PTSD group in the right temporal lobe (parahippocampal gyrus, middle temporal lobe), compared to the HC group. GM volume within the right temporal lobe cluster negatively correlated with CAPS-5 scores and MAD scores in the PTSD group. Conclusion: Results suggest that patients with PTSD with reduced GM volume in the right temporal regions (parahippocampal gyrus) experienced greater symptom severity and showed more AD-like brain activity. These results show potential for early identification of those who may be at an increased risk for future development of dementia. [ABSTRACT FROM AUTHOR]

Rotator cuff calcific tendinopathy and arthrofibrosis of the shoulder (adhesive capsulitis) are debilitating musculoskeletal disorders that significantly impact joint function and impair quality of life. Despite its high prevalence and common clinical presentation, the metabolic mechanisms underlying these conditions characterized by pain, and reduced mobility, remain poorly understood. This review aims to elucidate the role of metabolic processes implicated in the pathogenesis of calcific tendinopathy and shoulder arthrofibrosis. We will be focusing on the mechanistic role of how these processes contribute to disease progression and can direct potential therapeutic targets. Calcific tendinopathy is marked by aberrant calcium deposition within tendons, influenced by disrupted calcium and phosphate homeostasis, and altered cellular responses. Key molecular pathways, including bone morphogenetic proteins (BMPs), Wnt signaling, and transforming growth factor-beta (TGF-β), play crucial roles in the pathophysiology of calcification, calcium imbalance, and muscle fibrosis. In contrast, shoulder arthrofibrosis involves excessive collagen deposition and fibrosis within the shoulder joint capsule, driven by metabolic dysregulation and inflammation. The TGF-β signaling pathway and inflammatory cytokines, such as interleukin-6 (IL-6), are central to the fibrotic response. A comparative analysis reveals both shared and distinct metabolic pathways between these conditions, highlighting the interplay between inflammation, cellular metabolism, extracellular matrix remodeling, calcific deposition, and calcium migration to the glenohumeral joints, resulting in adhesive capsulitis, thereby providing insights into their pathophysiology. This review discusses current therapeutic approaches and their limitations, advocating for the development of targeted therapies that address specific metabolic dysregulations. Future therapeutic strategies focus on developing targeted interventions that address the underlying metabolic dysregulation, aiming to improve patient outcomes and advance clinical management. This review offers a comprehensive overview of the metabolic mechanisms involved in calcific tendinopathy and shoulder arthrofibrosis, providing a foundation for future research and therapeutic development. [ABSTRACT FROM AUTHOR]

Introduction: Inadequate exposure to real-life operating can impede timely acquisition of technical competence among surgical residents, and is a major challenge faced in the current training climate. Mental rehearsal (MR)—the cognitive rehearsal of a motor task without overt physical movement—has been shown to accelerate surgical skills learning. However, the neuroplastic effect of MR of a complex bimanual surgical task is unknown. The aim of this study is to use functional near-infrared spectroscopy (fNIRS) to assess the impact of MR on prefrontal and motor cortical activation during a laparoscopic knot tying task. Methods: Twelve surgical residents performed a laparoscopic knot tying task before and after either mental rehearsal (MR, intervention group) or textbook reading (TR, control group). In both groups, fNIRS was used to measure changes in oxygenated hemoglobin concentration (HbO2) in the prefrontal (24 channels) and motor cortices (22 channels). Technical performance was measured using leak volume, objective performance score and task progression score. Results: MR led to a decrease in HbO2 (reduced activation) in the bilateral prefrontal cortex (PFC), and an increase in HbO2 (increased activation) in the left middle frontal gyrus, left precentral gyrus, and left postcentral gyrus. No discernible changes in activation were observed after TR in either the PFC or motor cortex. Moreover, smaller ΔHbO2 responses in the right PFC and greater ΔHbO2 responses in the left motor cortex were observed in the MR group compared with the TR group. Leak volume was significantly less following MR (p = 0.019), but not after TR (p = 0.347). Mean objective performance score was significantly higher following MR compared with TR (p = 0.043). Conclusion: Mental rehearsal may enhance surgical skill acquisition and technical proficiency by reducing utilization of attentional resources in the prefrontal cortex and improving neural efficiency in motor areas during a laparoscopic surgical task. [ABSTRACT FROM AUTHOR]

The use of genome-scale sequencing allows for identification of genetic findings beyond the original indication for testing (secondary findings). The ClinGen Actionability Working Groups (AWG) protocol for evidence synthesis and semi-quantitative metric scoring evaluates four domains of clinical actionability for potential secondary findings: severity and likelihood of the outcome, and effectiveness and nature of the intervention. As of February 2018, the AWG has scored 127 genes associated with 78 disorders (up-to-date topics/scores are available at www.clinicalgenome.org). Scores across these disorders were assessed to compare genes/disorders recommended for return as secondary findings by the American College of Medical Genetics and Genomics (ACMG) with those not currently recommended. Disorders recommended by the ACMG scored higher on outcome-related domains (severity and likelihood), but not on intervention-related domains (effectiveness and nature of the intervention). Current practices indicate that return of secondary findings will expand beyond those currently recommended by the ACMG. The ClinGen AWG evidence reports and summary scores are not intended as classifications of actionability, rather they provide a resource to aid decision makers as they determine best practices regarding secondary findings. The ClinGen AWG is working with the ACMG Secondary Findings Committee to update future iterations of their secondary findings list.