Emergence of an early SARS-CoV-2 epidemic in the United States.

The emergence of the COVID-19 epidemic in the United States (U.S.) went largely undetected due to inadequate testing. New Orleans experienced one of the earliest and fastest accelerating outbreaks, coinciding with Mardi Gras. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large-scale events accelerate transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana had limited diversity compared to other U.S. states and that one introduction of SARS-CoV-2 led to almost all of the early transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras, and the festival dramatically accelerated transmission. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate epidemics.

Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States.

The novel coronavirus SARS-CoV-2 was first detected in the Pacific Northwest region of the United States in January 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the United States, we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated effects of federal travel restrictions. This study provides evidence of widespread sustained transmission of SARS-CoV-2 within the United States and highlights the critical need for local surveillance.

Travel Surveillance and Genomics Uncover a Hidden Zika Outbreak during the Waning Epidemic.

The Zika epidemic in the Americas has challenged surveillance and control. As the epidemic appears to be waning, it is unclear whether transmission is still ongoing, which is exacerbated by discrepancies in reporting. To uncover locations with lingering outbreaks, we investigated travel-associated Zika cases to identify transmission not captured by reporting. We uncovered an unreported outbreak in Cuba during 2017, a year after peak transmission in neighboring islands. By sequencing Zika virus, we show that the establishment of the virus was delayed by a year and that the ensuing outbreak was sparked by long-lived lineages of Zika virus from other Caribbean islands. Our data suggest that, although mosquito control in Cuba may initially have been effective at mitigating Zika virus transmission, such measures need to be maintained to be effective. Our study highlights how Zika virus may still be "silently" spreading and provides a framework for understanding outbreak dynamics. VIDEO ABSTRACT.

Unlocking the future of patient Education: ChatGPT vs. LexiComp® as sources of patient education materials.

BACKGROUND: ChatGPT is a conversational artificial intelligence technology that has shown application in various facets of healthcare. With the increased use of AI, it is imperative to assess the accuracy and comprehensibility of AI platforms. OBJECTIVE: This pilot project aimed to assess the understandability, readability, and accuracy of ChatGPT as a source of medication-related patient education as compared with an evidence-based medicine tertiary reference resource, LexiComp®. METHODS: Patient education materials (PEMs) were obtained from ChatGPT and LexiComp® for 8 common medications (albuterol, apixaban, atorvastatin, hydrocodone/acetaminophen, insulin glargine, levofloxacin, omeprazole, and sacubitril/valsartan). PEMs were extracted, blinded, and assessed by 2 investigators independently. The primary outcome was a comparison of the Patient Education Materials Assessment Tool-printable (PEMAT-P). Secondary outcomes included Flesch reading ease, Flesch Kincaid grade level, percent passive sentences, word count, and accuracy. A 7-item accuracy checklist for each medication was generated by expert consensus among pharmacist investigators, with LexiComp® PEMs serving as the control. PEMAT-P interrater reliability was determined via intraclass correlation coefficient (ICC). Flesch reading ease, Flesch Kincaid grade level, percent passive sentences, and word count were calculated by Microsoft® Word®. Continuous data were assessed using the Student's t-test via SPSS (version 20.0). RESULTS: No difference was found in the PEMAT-P understandability score of PEMs produced by ChatGPT versus LexiComp® [77.9% (11.0) vs. 72.5% (2.4), P=0.193]. Reading level was higher with ChatGPT [8.6 (1.2) vs. 5.6 (0.3), P < 0.001). ChatGPT PEMs had a lower percentage of passive sentences and lower word count. The average accuracy score of ChatGPT PEMs was 4.25/7 (61%), with scores ranging from 29% to 86%. CONCLUSION: Despite comparable PEMAT-P scores, ChatGPT PEMs did not meet grade level targets. Lower word count and passive text with ChatGPT PEMs could benefit patients, but the variable accuracy scores prevent routine use of ChatGPT to produce medication-related PEMs at this time.

The Influence of Kynurenine Metabolites on Neurodegenerative Pathologies.

As the kynurenine pathway's links to inflammation, the immune system, and neurological disorders became more apparent, it attracted more and more attention. It is the main pathway through which the liver breaks down Tryptophan and the initial step in the creation of nicotinamide adenine dinucleotide (NAD+) in mammals. Immune system activation and the buildup of potentially neurotoxic substances can result from the dysregulation or overactivation of this pathway. Therefore, it is not shocking that kynurenines have been linked to neurological conditions (Depression, Parkinson's, Alzheimer's, Huntington's Disease, Schizophrenia, and cognitive deficits) in relation to inflammation. Nevertheless, preclinical research has demonstrated that kynurenines are essential components of the behavioral analogs of depression and schizophrenia-like cognitive deficits in addition to mediators associated with neurological pathologies due to their neuromodulatory qualities. Neurodegenerative diseases have been extensively associated with neuroactive metabolites of the kynurenine pathway (KP) of tryptophan breakdown. In addition to being a necessary amino acid for protein synthesis, Tryptophan is also transformed into the important neurotransmitters tryptamine and serotonin in higher eukaryotes. In this article, a summary of the KP, its function in neurodegeneration, and the approaches being used currently to target the route therapeutically are discussed.

A wearable device-enabled therapeutic approach to improve joint attention in autism spectrum disorder: a prospective pilot study.

It has been previously proposed that interventions aimed at integrating and co-activating music processing and motor control systems could have therapeutic potential for priming social skill development in children with autism spectrum disorder (ASD). In this study, we assessed this hypothesis through a wearable sensor platform called Ambulosono ("Ambulo"-walk; "sono"-sound) in which pleasurable children's musical stimuli are contingently linked to effortful motor action (locomotor step size), thus creating a motivational state proposed to be conducive to joint attention (JA) operation. Five participants were recruited from a community-based partner and were assessed by scoring responses following therapist-directed bids for JA. Multiple assessment sessions through a repeated time-series design were conducted to determine baseline and post-intervention scores. The intervention session consisted of approximately 15 min of Ambulosono exposure. Baseline and post-intervention data were aggregated and analyzed using a linear mixed-effect model. The wearable sensor and wireless headphones of the Ambulosono system were tolerated by the participants, and there were no adverse effects associated with the use of the device. We found an increase in the average responses to bids for JA during the Ambulosono intervention phase compared to baseline across participants. This increase did not appear to result from enhanced general arousal. Our pilot data support feasibility and further testing of Ambulosono as a therapeutic aid for integration into community-based ASD programs to augment shared child-therapist social interactions.

Peripheral circadian gene activity is altered during hibernation in the thirteen-lined ground squirrel.

Many small mammals living in seasonally cold environments rely on hibernation, utilizing strong metabolic rate suppression and a slow consumption of adipose reserves to survive the winter months. The circannual rhythm of hibernation is well known but less is known about the role of the circadian clock while animals are in torpor for weeks at a time. We hypothesized that due to strong global suppression of transcription and translation in the torpid state, that circadian clock activity would likewise be suppressed in peripheral tissues during hibernation. However, the present study indicates that peripheral circadian clock activity persists during torpor. Using 13-lined ground squirrels (Ictidomys tridecemlineatus) as the model, this study analyzed transcript and protein responses by clock components, comparing euthermic control animals with squirrels in deep torpor for >3 days (subcutaneous body temperature 5-8 °C). The data show tissue specific responses by mRNA transcript levels: (a) no significant changes in transcript abundance in liver of control versus torpid squirrels, (b) a strong increase in Nr1d1 levels in white adipose during torpor, and (c) five significant transcript changes in skeletal muscle during torpor (increased Bmal1, Clock, Cry1 and Nr1d1 but decreased Per1). Levels of core clock proteins (BMAL1, CRY2, PER2, and casein kinases CK1δ and CK1ε) were also assessed across five time points of the torpor/arousal cycle showing both tissue- and time-dependent changes in clock proteins that were most prominent in liver and white adipose and indicating that peripheral clocks are still active in tissues over the torpor/arousal cycle.

Development and Validation of Ambulosono: A Wearable Sensor for Bio-Feedback Rehabilitation Training.

Wearable technology-based measurement systems hold potential for the therapeutic and rehabilitation management of patients with various chronic diseases. The purpose of this study was to assess the accuracy and test⁻retest reliability of a new-generation wearable sensor-based system, dubbed Ambulosono, for bio-feedback training. The Ambulosono sensor system was cross-validated by comparing its functionality with the iPod touch (4th generation) sensor system. Fifteen participants underwent a gait test to measure various gait parameters while wearing both the iPod-based and Ambulosono sensors simultaneously. The physically measured values (i.e., the true values) of step length, distance traveled, velocity, and cadence were then compared to those obtained via the two-sensor systems using the same calculation algorithms. While the mean percentage error was <10% for all measured parameters, and the intra-class correlation coefficient revealed a high level of agreement between trials for both sensor systems, it was found that the Ambulosono sensor system outperformed the iPod-based system in some respects. The Ambulosono sensor system possessed both reliability and accuracy in obtaining gait parameter measurements, which suggests it can serve as an economical alternative to the iPod-based system that is currently used in various clinical rehabilitation programs.

International travel between global urban centres vulnerable to yellow fever transmission.

OBJECTIVE: To examine the potential for international travel to spread yellow fever virus to cities around the world. METHODS: We obtained data on the international flight itineraries of travellers who departed yellow fever-endemic areas of the world in 2016 for cities either where yellow fever was endemic or which were suitable for viral transmission. Using a global ecological model of dengue virus transmission, we predicted the suitability of cities in non-endemic areas for yellow fever transmission. We obtained information on national entry requirements for yellow fever vaccination at travellers' destination cities. FINDINGS: In 2016, 45.2 million international air travellers departed from yellow fever-endemic areas of the world. Of 11.7 million travellers with destinations in 472 cities where yellow fever was not endemic but which were suitable for virus transmission, 7.7 million (65.7%) were not required to provide proof of vaccination upon arrival. Brazil, China, India, Mexico, Peru and the United States of America had the highest volumes of travellers arriving from yellow fever-endemic areas and the largest populations living in cities suitable for yellow fever transmission. CONCLUSION: Each year millions of travellers depart from yellow fever-endemic areas of the world for cities in non-endemic areas that appear suitable for viral transmission without having to provide proof of vaccination. Rapid global changes in human mobility and urbanization make it vital for countries to re-examine their vaccination policies and practices to prevent urban yellow fever epidemics.

Ghrelin enhances cue-induced bar pressing for high fat food.

Ghrelin is an orexigenic hormone produced by the stomach that acts on growth hormone secretagogue receptors (GHSRs) both peripherally and centrally. The presence of GHSRs in the ventral tegmental area (VTA) suggests that ghrelin signaling at this level may increase the incentive value of palatable foods as well as other natural and artificial rewards. The present investigation sought to determine if ghrelin plays a role in relapse to such foods following a period of abstinence. To achieve this, thirty-six male Long Evans rats were trained to press a lever to obtain a high fat chocolate food reward on a fixed ratio schedule of 1. Following an extinction period during which lever presses were not reinforced, rats were implanted with a cannula connected to a minipump that continuously delivered ghrelin, a GHSR antagonist ([d-Lys-3]-GHRP-6), or saline in the VTA for 14days. One week later, food reward-associated cues, food reward priming, and an overnight fast were used to induce reinstatement of the lever pressing response. Our results indicate that intra-VTA ghrelin enhances cue-induced reinstatement of responses for palatable food pellets. To the extent that the reinstatement paradigm is considered a valid model of relapse in humans, this suggests that ghrelin signaling facilitates relapse to preferred foods in response to food cues through GHSR signaling in the VTA.

Projected Zika Virus Importation and Subsequent Ongoing Transmission after Travel to the 2016 Olympic and Paralympic Games - Country-Specific Assessment, July 2016.

Zika virus belongs to the genus Flavivirus of the family Flaviviridae; it is transmitted to humans primarily through the bite of an infected Aedes species mosquito (e.g., Ae. aegypti and Ae. albopictus) (1). Zika virus has been identified as a cause of congenital microcephaly and other serious brain defects (2). As of June 30, 2016, CDC had issued travel notices for 49 countries and U.S. territories across much of the Western hemisphere (3), including Brazil, where the 2016 Olympic and Paralympic Games (Games of the XXXI Olympiad, also known as Rio 2016; Games) will be hosted in Rio de Janeiro in August and September 2016. During the Games, mosquito-borne Zika virus transmission is expected to be low because August and September are winter months in Brazil, when cooler and drier weather typically reduces mosquito populations (4). CDC conducted a risk assessment to predict those countries susceptible to ongoing Zika virus transmission resulting from introduction by a single traveler to the Games. Whereas all countries are at risk for travel-associated importation of Zika virus, CDC estimated that 19 countries currently not reporting Zika outbreaks have the environmental conditions and population susceptibility to sustain mosquito-borne transmission of Zika virus if a case were imported from infection at the Games. For 15 of these 19 countries, travel to Rio de Janeiro during the Games is not estimated to increase substantially the level of risk above that incurred by the usual aviation travel baseline for these countries. The remaining four countries, Chad, Djibouti, Eritrea, and Yemen, are unique in that they do not have a substantial number of travelers to any country with local Zika virus transmission, except for anticipated travel to the Games. These four countries will be represented by a projected, combined total of 19 athletes (plus a projected delegation of about 60 persons), a tiny fraction of the 350,000-500,000 visitors expected at the Games.* Overall travel volume to the Games represents a very small fraction (<0.25%) of the total estimated 2015 travel volume to Zika-affected countries,(†) highlighting the unlikely scenario that Zika importation would be solely attributable to travel to the Games. To prevent Zika virus infection and its complications among athletes and visitors to the Games and importation of Zika virus into countries that could sustain local transmission, pregnant women should not travel to the Games, mosquito bites should be avoided while traveling and for 3 weeks after returning home, and measures should be taken to prevent sexual transmission (Box).

A survey on awareness, knowledge and preferences toward genetic testing among the United States general public.

Aim: To understand awareness, knowledge and preferences regarding genetic testing among the USA general public. Methods: A cross-sectional online survey using a Qualtrics Panel. Results: Among 1600 respondents, 545 (34%) were White, 411 (26%) Black, 412 (26%) Hispanic or Latin(x) and 232 (15%) Asian. Most had heard of ancestry testing (87%) and genetic health risk testing (69%), but a third thought inherited genes were only a little or not at all responsible for obesity (36%) and mental health (33%). The majority preferred pre-emptive pharmacogenetic testing (n = 74%) compared with reactive testing. Statistically significant differences between racial/ethnic groups and rural-urban respondents were observed. Conclusion: Most preferred pre-emptive pharmacogenetic testing; however, about one-quarter preferred reactive testing. Preferences should be discussed during patient-clinician interactions.

What is this study about? This study presents a large online survey among the USA general public to understand their awareness, knowledge and preferences about genetic testing and how this may vary by racial/ethnic group and rural/urban status.What were the results? Most survey respondents had heard of ancestry testing (87%) and genetic health risk testing (69%). However, over a third of respondents thought that inherited genes may be only a little or not at all responsible for obesity (36%) and mental health (33%). When asked about preferences for pre-emptive compared with reactive pharmacogenetic testing, the majority preferred pre-emptive testing (n = 74%). Statistically significant differences between racial/ethnic groups as well as rural-urban respondents were seen.What do the results mean? The US general public may have a different understanding of genetic testing for different diseases, and have different preferences when it comes to the timing of testing. Appropriate educational content targeting the link between genetics and specific diseases should be prepared, and preferences for pre-emptive or reactive testing should be discussed during visits with healthcare providers.

Assessing effects of Cannabis on various neuropathologies: A systematic review.

Natural bioactives possess a wide range of chemical structures that can exert a plethora of pharmacological and toxicological actions, resulting in neuroprotection or neurotoxicity. These pharmacodynamic properties can positively or negatively impact human and animal global healthcare. Remarkably, Ayurvedic botanical Cannabis has been used worldwide by different ethnicities and religions for spiritual, commercial, recreational, nutraceutical, cosmeceutical, and medicinal purposes for centuries. Cannabis-based congeners have been approved by the United States of America's (USA) Food & Drug Administration (FDA) and other global law agencies for various therapeutic purposes. Surprisingly, the strict laws associated with possessing cannabis products have been mitigated in multiple states in the USA and across the globe for recreational use. This has consequently led to a radical escalation of exposure to cannabis-related substances of abuse. However, there is a lacuna in the literature on the acute and chronic effects of Cannabis and its congeners on various neuropathologies. Moreover, in the post-COVID era, there has been a drastic increase in the incidence and prevalence of numerous neuropathologies, leading to increased morbidity and mortality. There is an impending necessity for a safe, economically viable, multipotent, natural bioactive to prevent and treat various neuropathologies. The ayurvedic herb, Cannabis is one of the oldest botanicals known to humans and has been widely used. However, the comprehensive effect of Cannabis on various neuropathologies is not well established. Hence, this review presents effects of Cannabis on various neuropathologies.

Projecting the future incidence and burden of dengue in Southeast Asia.

The recent global expansion of dengue has been facilitated by changes in urbanisation, mobility, and climate. In this work, we project future changes in dengue incidence and case burden to 2099 under the latest climate change scenarios. We fit a statistical model to province-level monthly dengue case counts from eight countries across Southeast Asia, one of the worst affected regions. We project that dengue incidence will peak this century before declining to lower levels with large variations between and within countries. Our findings reveal that northern Thailand and Cambodia will show the biggest decreases and equatorial areas will show the biggest increases. The impact of climate change will be counterbalanced by income growth, with population growth having the biggest influence on increasing burden. These findings can be used for formulating mitigation and adaptation interventions to reduce the immediate growing impact of dengue virus in the region.

Using spatial and population mobility models to inform outbreak response approaches in the Ebola affected area, Democratic Republic of the Congo, 2018-2020.

The Democratic Republic of the Congo's (DRC) 10th known Ebola virus disease (EVD) outbreak occurred between August 1, 2018 and June 25, 2020, and was the largest EVD outbreak in the country's history. During this outbreak, the DRC Ministry of Health initiated traveller health screening at points of control (POC, locations not on the border) and points of entry (POE) to minimize disease translocation via ground and air travel. We sought to develop a model-based approach that could be applied in future outbreaks to inform decisions for optimizing POC and POE placement, and allocation of resources more broadly, to mitigate the risk of disease translocation associated with ground-level population mobility. We applied a parameter-free mobility model, the radiation model, to estimate likelihood of ground travel between selected origin locations (including Beni, DRC) and surrounding population centres, based on population size and drive-time. We then performed a road network route analysis and included estimated population movement results to calculate the proportionate volume of travellers who would move along each road segment; this reflects the proportion of travellers that could be screened at a POC or POE. For Beni, the road segments estimated to have the highest proportion of travellers that could be screened were part of routes into Uganda and Rwanda. Conversely, road segments that were part of routes to other population centres within the DRC were estimated to have relatively lower proportions. We observed a posteriori that, in many instances, our results aligned with locations that were selected for actual POC or POE placement through more time-consuming methods. This study has demonstrated that mobility models and simple spatial techniques can help identify potential locations for health screening at newly placed POC or existing POE during public health emergencies based on expected movement patterns. Importantly, we have provided methods to estimate the proportionate volume of travellers that POC or POE screening measures would assess based on their location. This is critical information in outbreak situations when timely decisions must be made to implement public health interventions that reach the most individuals across a network.

Patient Reported Outcomes of Transperineal Prostate Biopsy With Tumescent Local Anesthesia.

OBJECTIVE: To report the outcomes of performing transperineal prostate biopsy in the office setting using the novel anesthetic technique of tumescent local anesthesia. We report anxiety, pain, and embarrassment of patients who underwent this procedure compared to patients who underwent a transrectal prostate biopsy using standard local anesthesia. MATERIALS AND METHODS: Consecutive patients undergoing either a transperineal prostate biopsy under tumescent local anesthesia or a transrectal prostate biopsy with standard local anesthetic technique were prospectively enrolled. The tumescent technique employed dilute lidocaine solution administered using a self-filling syringe. Patients were asked to rate their pain before, during, and after their procedure using a visual analog scale. Patient anxiety and embarrassment was assessed using the Testing Modalities Index Questionnaire. RESULTS: Between April 2021 and June 2022, 430 patients underwent a transperineal prostate biopsy using tumescent local anesthesia and 65 patients underwent a standard transrectal prostate biopsy. Patients who underwent a transperineal biopsy had acceptable but significantly higher pain scores than those who underwent a transrectal prostate biopsy (3.9 vs 1.6, P-value <.01). These scores fell to almost zero immediately following their procedure. Additionally, transperineal biopsy patients were more likely to experience anxiety (71% vs 45%, P < .01) and embarrassment (32% vs 15%, P < .01). CONCLUSION: Transperineal biopsy using local tumescent anesthesia is safe and well-tolerated. Despite the benefits, patients undergoing a transperineal prostate biopsy under tumescent anesthesia still experienced worse procedural pain, anxiety, and embarrassment. Additional studies examining other adjunctive interventions to improve patient experience during transperineal prostate biopsy are needed.

Regional connectivity drove bidirectional transmission of SARS-CoV-2 in the Middle East during travel restrictions.

Regional connectivity and land travel have been identified as important drivers of SARS-CoV-2 transmission. However, the generalizability of this finding is understudied outside of well-sampled, highly connected regions. In this study, we investigated the relative contributions of regional and intercontinental connectivity to the source-sink dynamics of SARS-CoV-2 for Jordan and the Middle East. By integrating genomic, epidemiological and travel data we show that the source of introductions into Jordan was dynamic across 2020, shifting from intercontinental seeding in the early pandemic to more regional seeding for the travel restrictions period. We show that land travel, particularly freight transport, drove introduction risk during the travel restrictions period. High regional connectivity and land travel also drove Jordan's export risk. Our findings emphasize regional connectedness and land travel as drivers of transmission in the Middle East.

Signal-to-noise optimization for sodium MRI of the human knee at 4.7 Tesla using steady state.

Sodium magnetic resonance imaging of knee cartilage is a possible diagnostic method for osteoarthritis, but low signal-to-noise ratio yields low spatial resolution images and long scan times. For a given scan time, a steady-state approach with reduced repetition time and increased averaging may improve signal-to-noise ratio and hence attainable resolution. However, repetition time reduction results in increased power deposition, which must be offset with increased radiofrequency pulse length and/or reduced flip angle to maintain an acceptable specific absorption rate. Simulations varying flip angle, repetition time, and radiofrequency pulse length were performed for constant power deposition corresponding to ∼6 W/kg over the human knee at 4.7 T. For 10% agar, simulation closely matched experiment. For healthy human knee cartilage, a 37% increase in signal-to-noise ratio was predicted for steady-state over "fully relaxed" parameters while a 29% ± 4% increase was determined experimentally (n=10). Partial volume of cartilage with synovial fluid, inaccurate relaxation parameters used in simulation, and/or quadrupolar splitting may be responsible for this disagreement. Excellent quality sodium images of the human knee were produced in 9 mins at 4.7 T using the signal-to-noise ratio enhancing steady-state technique.