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\"Having lived nearly her entire life below the poverty line before going on to attain wealth and success as an entrepreneur and investor, Arlan Hamilton knows that entrepreneurship is the quickest path to money and power--particularly for those who haven't had much of it in the past. In Your First Million, she shows how anyone--no matter what they look like or how much money they have--can tap into all the new tools they already have at their disposal to get their million-dollar idea off the ground. Readers will learn: how to identify unmet needs, raise money, choose the right collaborators, create multiple income streams, and turn their unique knowledge and experience into a profitable businesses--while reinvesting in their communities and empowering others to do the same. If we can change who gets to decide what new ideas are worthy, and who gets to turn those ideas into reality, not only can we change our own circumstances--we can change the world\"-- Provided by publisher.

By uncovering complex dynamics in the expression or localization of transcriptional regulators in single cells that were otherwise hidden at the population level, live cell imaging has transformed our understanding of how cells sense and orchestrate appropriate responses to changes in their internal state or extracellular environment. This has proved particularly true for the nuclear factor-kappaB (NF-κB) family of transcription factors, key regulators of the inflammatory response and innate immune function, which are capable of encoding information about the mode and intensity of stimuli in the dynamics of NF-κB nuclear accumulation and loss. While live cell imaging continues to serve as a useful tool in ongoing efforts to characterize the feedbacks that shape these dynamics and to connect dynamics to downstream gene expression, it is also proving invaluable for recent studies that seek to determine how intracellular pathogens subvert NF-κB signaling to survive and replicate within host cells by providing quantitative information about the pathogen and changes in NF-κB activity during different stages of an infection. Here, we provide a brief overview of NF-κB signaling in innate immune cells and review recent literature that uses live imaging to investigate the mechanisms by which bacterial and yeast pathogens modulate NF-κB in a variety of different host cell types to evade destruction or maintain the viability of an intracellular growth niche.

Monitoring the spread of SARS-CoV-2 and reconstructing transmission chains has become a major public health focus for many governments around the world. The modest mutation rate and rapid transmission of SARS-CoV-2 prevents the reconstruction of transmission chains from consensus genome sequences, but within-host genetic diversity could theoretically help identify close contacts. Here we describe the patterns of within-host diversity in 1181 SARS-CoV-2 samples sequenced to high depth in duplicate. 95.1% of samples show within-host mutations at detectable allele frequencies. Analyses of the mutational spectra revealed strong strand asymmetries suggestive of damage or RNA editing of the plus strand, rather than replication errors, dominating the accumulation of mutations during the SARS-CoV-2 pandemic. Within- and between-host diversity show strong purifying selection, particularly against nonsense mutations. Recurrent within-host mutations, many of which coincide with known phylogenetic homoplasies, display a spectrum and patterns of purifying selection more suggestive of mutational hotspots than recombination or convergent evolution. While allele frequencies suggest that most samples result from infection by a single lineage, we identify multiple putative examples of co-infection. Integrating these results into an epidemiological inference framework, we find that while sharing of within-host variants between samples could help the reconstruction of transmission chains, mutational hotspots and rare cases of superinfection can confound these analyses. The COVID-19 pandemic has had major health impacts across the globe. The scientific community has focused much attention on finding ways to monitor how the virus responsible for the pandemic, SARS-CoV-2, spreads. One option is to perform genetic tests, known as sequencing, on SARS-CoV-2 samples to determine the genetic code of the virus and to find any differences or mutations in the genes between the viral samples. Viruses mutate within their hosts and can develop into variants that are able to more easily transmit between hosts. Genetic sequencing can reveal how genetically similar two SARS-CoV-2 samples are. But tracking how SARS-CoV-2 moves from one person to the next through sequencing can be tricky. Even a sample of SARS-CoV-2 viruses from the same individual can display differences in their genetic material or within-host variants. Could genetic testing of within-host variants shed light on factors driving SARS-CoV-2 to evolve in humans? To get to the bottom of this, Tonkin-Hill, Martincorena et al. probed the genetics of SARS-CoV-2 within-host variants using 1,181 samples. The analyses revealed that 95.1% of samples contained within-host variants. A number of variants occurred frequently in many samples, which were consistent with mutational hotspots in the SARS-CoV-2 genome. In addition, within-host variants displayed mutation patterns that were similar to patterns found between infected individuals. The shared within-host variants between samples can help to reconstruct transmission chains. However, the observed mutational hotspots and the detection of multiple strains within an individual can make this challenging. These findings could be used to help predict how SARS-CoV-2 evolves in response to interventions such as vaccines. They also suggest that caution is needed when using information on within-host variants to determine transmission between individuals.

Giant cell arteritis (GCA) is a serious condition that carries with it a high rate of morbidity. This review highlights the pearls and pitfalls of GCA in adult patients, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. GCA is an immune-mediated vasculitis of medium-sized vessels that primarily affects those over the age of 50 years. Patients can present with a variety of signs and symptoms, including headache, vision changes, and systemic findings such as fever. Findings including jaw and limb claudication, vision changes, and temporal artery abnormalities are specific for diagnosis. While there are no highly sensitive features of the history and examination, the disease should be suspected in patients over the age of 50 years with vision changes, new headache, temporal artery abnormalities, or jaw claudication, especially in the setting of systemic symptoms. Inflammatory markers including erythrocyte sedimentation rate and c-reactive protein in combination are sensitive but not specific for GCA. Delay in diagnosis is associated with vision loss and other complications including aortitis. If suspected, the emergency physician should administer steroids and consult the ophthalmology and rheumatology specialists. An understanding of GCA can assist emergency clinicians in diagnosing and managing this potentially dangerous disease.

Prior research has demonstrated the widespread presence of racial disparities in emergency department (ED) care and analgesia. We hypothesized that racial disparities continue to exist in ED analgesic prescribing patterns, time to analgesia, and time to provider in the treatment of headache. We performed a retrospective cohort study of patients presenting to a large tertiary academic ED with chief complaint of headache. A structured medical record review was conducted to abstract relevant variables of interest. Patient race was categorized as white or Black, Indigenous, or person of color (BIPOC). Descriptive statistics were used to characterize the cohort and stratified analyses were conducted based on patient race and our key outcome measures of analgesic prescribing patterns, time to analgesia, and time to provider in the treatment of headache. White patients were more likely to be assigned an Emergency Severity Index score 2 or 3 and their BIPOC counterparts were more likely to be assigned an ESI score 3 or 4 (p = 0.02). There was no significant difference by race in time to analgesia (p = 0.318), time to provider (p = 0.358), or time to first medication treatment (p = 0.357). However, there were clear differences in prescribing patterns. BIPOC patients were significantly more likely to be treated with acetaminophen (p = 0.042) or ibuprofen (p = 0.015) despite reporting higher pain levels during triage (p < 0.001). White patients were significantly more likely to receive a head CT scan (p < 0.001) or neurology consult (p = 0.003) than their BIPOC counterparts. Racial disparities persist in assessment and type of analgesia for patients being treated for headache in a large academic emergency department.

Spasticity and gait impairments are two common disabilities after cervical spinal cord injury (C-SCI). In this study, we tested the therapeutic effects of early treadmill locomotor training (Tm) initiated at postoperative (PO) day 8 and continued for 6 weeks with injury site transcranial magnetic stimulation (TMSsc) on spasticity and gait impairments after low C6/7 moderate contusion C-SCI in a rat model. The combined treatment group (Tm+TMSsc) showed the most robust decreases in velocity-dependent ankle torques and triceps surae electromyography burst amplitudes that were time locked to the initial phase of lengthening, as well as the most improvement in limb coordination quantitated using three-dimensional kinematics and CatWalk gait analyses, compared to the control or single-treatment groups. These significant treatment-associated decreases in measures of spasticity and gait impairment were also accompanied by marked treatment-associated up-regulation of dopamine beta-hydroxylase, glutamic acid decarboxylase 67, gamma-aminobutyric acid B receptor, and brain-derived neurotrophic factor in the lumbar spinal cord (SC) segments of the treatment groups, compared to tissues from the C-SCI nontreated animals. We propose that the treatment-induced up-regulation of these systems enhanced the adaptive plasticity in the SC, in part through enhanced expression of pre- and postsynaptic reflex regulatory processes. Further, we propose that locomotor exercise in the setting of C-SCI may decrease aspects of the spontaneous maladaptive segmental and descending plasticity. Accordingly, TMSsc treatment is characterized as an adjuvant stimulation that may further enhance this capacity. These data are the first to suggest that a combination of Tm and TMSsc across the injury site can be an effective treatment modality for C-SCI-induced spasticity and gait impairments and provided a pre-clinical demonstration for feasibility and efficacy of early TMSsc intervention after C-SCI.

Abstract Dissemination and implementation (D&I) researchers serve critical scientific, practical, and personal roles in translating science to public health benefit. However, they face multifaceted barriers that may erode their capacity to plan, lead, and evaluate implementation. Individualized coaching focused on human flourishing is an unexplored approach to fully actualize D&I researchers’ capacity to bridge the research-practice gap. The purpose of this exploratory pilot study was to investigate a tailored coaching program to support human flourishing among D&I researchers. A pragmatic, mixed-methods approach guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) Framework was used to evaluate an individualized, nine session coaching program called FUEL (Focus, Unplug, Exercise, Love). Reach and Implementation were assessed through descriptive statistics and rapid qualitative analysis of surveys and coaching logs. Effectiveness and Maintenance were assessed through descriptive statistics and iterative content analysis of participant surveys, as well as iterative content analysis of proxy (e.g., colleague) semi-structured interviews. Reach results indicated that demand for coaching exceeded study enrollment capacity (n = 16 participants). Implementation results showed that the coach spent 12.96 ± 2.82 hr per participant over 3 months. Effectiveness and Maintenance results indicated that FUEL was well-received and provided participants with myriad psychological and professional benefits. Preliminary evidence suggests that the FUEL coaching program is a promising and feasible approach to enhance flourishing among D&I researchers. Future research is needed to evaluate Adoption and scalability. This pilot study may inform future D&I capacity-building initiatives that address researchers’ holistic situatedness within the implementation process. Researchers serve vital roles in translating science to public health benefit. However, a variety of issues, including personal well-being, may reduce researchers’ capacity to bridge the research-practice gap. The purpose of this study was to explore an individualized, one-on-one, nine session coaching program to support health researchers’ holistic well-being and life quality as they strive to advance others’ health. The coaching program was called FUEL (Focus, Unplug, Exercise, Love). The RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) Framework was used to evaluate the program. Sixteen researchers from around the United States participated in the study. Results indicate that (1) demand for coaching exceeded study enrollment capacity, (2) the coach spent a total of approximately 13 hours with each participant over three months, and (3) participants experienced a variety of psychological and professional benefits. Overall, this study provides preliminary evidence that individualized coaching is a well-received, feasible approach to improve health researchers’ holistic well-being, ultimately optimizing their capacity to advance public health. Future research is needed to reach a more diverse population and to examine scalability.