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While it is widely accepted that motor sequence learning (MSL) is supported by a prefrontal-mediated interaction between hippocampal and striatal networks, it remains unknown whether the functional responses of these networks can be modulated in humans with targeted experimental interventions. The present proof-of-concept study employed a multimodal neuroimaging approach, including functional magnetic resonance (MR) imaging and MR spectroscopy, to investigate whether individually-tailored theta-burst stimulation of the dorsolateral prefrontal cortex can modulate responses in the hippocampus and the basal ganglia during motor learning. Our results indicate that while stimulation did not modulate motor performance nor task-related brain activity, it influenced connectivity patterns within hippocampo-frontal and striatal networks. Stimulation also altered the relationship between the levels of gamma-aminobutyric acid (GABA) in the stimulated prefrontal cortex and learning-related changes in both activity and connectivity in fronto-striato-hippocampal networks. This study provides the first experimental evidence, to the best of our knowledge, that brain stimulation can alter motor learning-related functional responses in the striatum and hippocampus.

BackgroundTransgender, nonbinary, and gender-diverse (TNG) youth encounter barriers to psychosocial wellness and also describe exploring identities and communities on the web. Studies of cisgender youth connect increased digital technology use with lower well-being, parent relationships, and body image scores as well as increased loneliness and fear of missing out (FOMO). However, little is known about the psychosocial factors associated with digital technology use among TNG compared with cisgender youth. ObjectiveThis study aims to examine the associations between psychosocial measures and digital technology use and its importance for cisgender and TNG youth. MethodsWe surveyed a nationally representative sample of adolescents (aged 13-18 years) about psychosocial wellness and digital technology use. Psychosocial measures included assessment of well-being, parental relationships, body image, loneliness, and FOMO. Digital media use assessments included the short Problematic and Risky Internet Use Screening Scale-3 and the Adolescent Digital Technology Interactions and Importance (ADTI) scale and subscales. We compared psychosocial measures between gender identity groups. We also compared stratified correlations for psychosocial measures (well-being, parent relationships, body image, loneliness, and FOMO) with ADTI and Problematic and Risky Internet Use Screening Scale-3 scores between gender identity groups. All comparisons were adjusted for age, race, and ethnicity. ResultsAmong 4575 adolescents, 53 (1.16%) self-identified as TNG youth. TNG youth had lower scores for well-being (23.76 vs 26.47; P

Objective Persistent post-COVID symptoms are estimated to occur in up to 10% of patients who have had COVID-19. These lingering symptoms may persist for weeks to months after resolution of the acute illness. This study aimed to add insight into our understanding of certain post-acute conditions and clinical findings. The primary purpose was to determine the persistent post COVID impairments prevalence and characteristics by collecting post COVID illness data utilizing Patient-Reported Outcomes Measurement Information System (PROMIS ® ). The resulting measures were used to assess surveyed patients physical, mental, and social health status. Methods A cross-sectional study and 6-months Mayo Clinic COVID recovered registry data were used to evaluate continuing symptoms severity among the 817 positive tested patients surveyed between March and September 2020. The resulting PROMIS ® data set was used to analyze patients post 30 days health status. The e-mailed questionnaires focused on fatigue, sleep, ability to participate in social roles, physical function, and pain. Results The large sample size (n = 817) represented post hospitalized and other managed outpatients. Persistent post COVID impairments prevalence and characteristics were determined to be demographically young (44 years), white (87%), and female (61%). Dysfunction as measured by the PROMIS ® scales in patients recovered from acute COVID-19 was reported as significant in the following domains: ability to participate in social roles (43.2%), pain (17.8%), and fatigue (16.2%). Conclusion Patient response on the PROMIS ® scales was similar to that seen in multiple other studies which used patient reported symptoms. As a result of this experience, we recommend utilizing standardized scales such as the PROMIS ® to obtain comparable data across the patients’ clinical course and define the disease trajectory. This would further allow for effective comparison of data across studies to better define the disease process, risk factors, and assess the impact of future treatments.

Objective To develop and implement criteria for description of post COVID syndrome based on analysis of patients presenting for evaluation at Mayo Clinic Rochester between November 2019 and August 2020. Methods A total of 465 patients with a history of testing positive for COVID-19 were identified and their medical records reviewed. After a thorough review, utilizing the DELPHI methods by an expert panel, 42 (9%) cases were identified with persistent central sensitization (CS) symptoms persisting after the resolution of acute COVID-19, herein referred to as Post COVID syndrome (PoCoS). In this report we describe the baseline characteristics of these PoCoS patients. Results Among these 42 PoCoS patients, the mean age was 46.2 years (median age was 46.5 years). Pain (90%), fatigue (74%), dyspnea (43%), and orthostatic intolerance (38%) were the most common symptoms. The characteristics of an initial 14 patients were utilized for the development of clinical criteria via a modified Delphi Method by a panel of experts in central sensitization disorders. These criteria were subsequently applied in the identification of 28 additional cases of suspected PoCoS. A 2-reviewer system was used to analyze agreement with using the criteria, with all 28 cases determined to be either probable or possible cases by the reviewers. Inter-reviewer agreement using these proposed defining criteria was high with a Cohen’s alpha of .88. Conclusions Here we present what we believe to be the first definitional criteria for Post COVID syndrome. These may be useful in clinical phenotyping of these patients for targeted treatment and future research.

Aims: Percutaneous mitral balloon valvotomy PMBV is an acceptable alternative to Mitral valve surgery for patients with mitral stenosis. The purpose of this study was to explore the immediate results of PMBV with respect to echocardiographic changes, outcomes, and complications, using a meta-analysis approach. Methods: MEDLINE, and EMBASE databases were searched (01/2012 to 10/2018) for original research articles regarding the efficacy and safety of PMBV. Two reviewers independently screened references for inclusion and abstracted data including article details and echocardiographic parameters before and 24–72 h after PMBV, follow-up duration, and acute complications. Disagreements were resolved by third adjudicator. Quality of all included studies was evaluated using the Newcastle-Ottawa Scale NOS. Results: 44/990 references met the inclusion criteria representing 6537 patients. Our findings suggest that PMBV leads to a significant increase in MVA (MD = 0.81 cm2; 0.76–0.87, p

Prion diseases are progressive, neurodegenerative diseases affecting humans and animals. Also known as the transmissible spongiform encephalopathies, for the hallmark spongiform change seen in the brain, these diseases manifest increased oxidative damage early in disease and changes in antioxidant enzymes in terminal brain tissue. Superoxide dismutase 2 (SOD2) is an antioxidant enzyme that is critical for life. SOD2 knock-out mice can only be kept alive for several weeks post-birth and only with antioxidant therapy. However, this results in the development of a spongiform encephalopathy. Consequently, we hypothesized that reduced levels of SOD2 may accelerate prion disease progression and play a critical role in the formation of spongiform change. Using SOD2 heterozygous knock-out and litter mate wild-type controls, we examined neuronal long-term potentiation, disease duration, pathology, and degree of spongiform change in mice infected with three strains of mouse adapted scrapie. No influence of the reduced SOD2 expression was observed in any parameter measured for any strain. We conclude that changes relating to SOD2 during prion disease are most likely secondary to the disease processes causing toxicity and do not influence the development of spongiform pathology.

Regular surveillance testing of asymptomatic individuals for SARS-CoV-2 has been center to SARS-CoV-2 outbreak prevention on college and university campuses. Here we describe the voluntary saliva testing program instituted at the University of California, Berkeley during an early period of the SARS-CoV-2 pandemic in 2020. The program was administered as a research study ahead of clinical implementation, enabling us to launch surveillance testing while continuing to optimize the assay. Results of both the testing protocol itself and the study participants' experience show how the program succeeded in providing routine, robust testing capable of contributing to outbreak prevention within a campus community and offer strategies for encouraging participation and a sense of civic responsibility.

Clinical and surveillance testing for the SARS-CoV-2 virus relies overwhelmingly on RT-qPCR-based diagnostics, yet several popular assays require 2–3 separate reactions or rely on detection of a single viral target, which adds significant time, cost, and risk of false-negative results. Furthermore, multiplexed RT-qPCR tests that detect at least two SARS-CoV-2 genes in a single reaction are typically not affordable for large scale clinical surveillance or adaptable to multiple PCR machines and plate layouts. We developed a RT-qPCR assay using the Luna Probe Universal One-Step RT-qPCR master mix with publicly available primers and probes to detect SARS-CoV-2 N gene, E gene, and human RNase P (LuNER) to address these shortcomings and meet the testing demands of a university campus and the local community. This cost-effective test is compatible with BioRad or Applied Biosystems qPCR machines, in 96 and 384-well formats, with or without sample pooling, and has a detection sensitivity suitable for both clinical reporting and wastewater surveillance efforts.

Saliva is an attractive specimen type for asymptomatic surveillance of COVID-19 in large populations due to its ease of collection and its demonstrated utility for detecting RNA from SARS-CoV-2. Multiple saliva-based viral detection protocols use a direct-to-RT-qPCR approach that eliminates nucleic acid extraction but can reduce viral RNA detection sensitivity. To improve test sensitivity while maintaining speed, we developed a robotic nucleic acid extraction method for detecting SARS-CoV-2 RNA in saliva samples with high throughput. Using this assay, the Free Asymptomatic Saliva Testing (IGI FAST) research study on the UC Berkeley campus conducted 11,971 tests on supervised self-collected saliva samples and identified rare positive specimens containing SARS-CoV-2 RNA during a time of low infection prevalence. In an attempt to increase testing capacity, we further adapted our robotic extraction assay to process pooled saliva samples. We also benchmarked our assay against nasopharyngeal swab specimens and found saliva methods require further optimization to match this gold standard. Finally, we designed and validated a RT-qPCR test suitable for saliva self-collection. These results establish a robotic extraction-based procedure for rapid PCR-based saliva testing that is suitable for samples from both symptomatic and asymptomatic individuals.

Previous research has consistently demonstrated that older adults have difficulties transforming recently learned movements into robust, long-lasting memories (i.e., motor memory consolidation). One potential avenue to enhance consolidation in older individuals is the administration of transcranial direct current stimulation (tDCS) to task-relevant brain regions after initial learning. Although this approach has shown promise, the underlying cerebral correlates have yet to be revealed. Moreover, it is unknown whether the effects of tDCS are lateralized, an open question with implications for rehabilitative approaches following predominantly unilateral neurological injuries. In this research, healthy older adults completed a sequential motor task before and 6 h after receiving anodal or sham stimulation to right or left primary motor cortex (M1) while functional magnetic resonance images were acquired. Unexpectedly, anodal stimulation to right M1 following left-hand sequence learning significantly hindered consolidation as compared to a sham control, whereas no differences were observed with left M1 stimulation following right-hand learning. Impaired performance following right M1 stimulation was paralleled by sustained engagement of regions known to be critical for early learning stages, including the caudate nucleus and the premotor and parietal cortices. Thus, post-learning tDCS in older adults not only exerts heterogenous effects across the two hemispheres but can also disrupt ongoing memory processing.

Background:. From a public health perspective, nasal surgery accounts for many unused opioids. Patients undergoing septorhinoplasty require few opioids, and efforts to eliminate this need may benefit both patients and the public. Methods:. A multimodal analgesic protocol consisting of 15 components encompassing all phases of care was implemented for 42 patients. Results:. Median age and BMI were 34 years and 23, respectively. Most were women (79%), White (79%), primary surgeries (62%), and self-pay (52%). Comorbid conditions were present in 74% of the patients, with anxiety (33%) and depression (21%) being the most common. Septoplasties (67%) and osteotomies (45%) were common. The median operative time was 70 minutes. No patients required opioids in recovery, and median time in recovery was 63 minutes. Ten (24%) patients required an opioid prescription after discharge. In those patients, median time to requirement was 27 hours (range 3–81), and median total requirement was 20 mg morphine equivalents (range 7.5–85). Protocol compliance inversely correlated to opioid use (P = 0.007). Compliance with local and regional anesthetic (20% versus 63%, P = 0.030) as well as ketorolac (70% versus 100%, P = 0.011) was lower in patients who required opioids. Patients who required opioids were less likely to be administered a beta blocker (0% versus 34%, P = 0.041). Pain scores were higher in opioid users on postoperative days 1–5 (P < 0.05). No complications occurred in those requiring opioids, and satisfaction rates were equivalent between groups. Conclusion:. This protocol allowed us to safely omit opioid prescriptions in 76% of patients following septorhinoplasty, without adverse effects on outcomes or patient satisfaction.

Human activities are changing ecosystems at an unprecedented rate, yet large-scale studies into how local human impacts alter natural systems and interact with other aspects of global change are still lacking. Here we provide empirical evidence that local human impacts fundamentally alter relationships between ecological communities and environmental drivers. Using tropical coral reefs as a study system, we investigated the influence of contrasting levels of local human impact using a spatially extensive dataset spanning 62 outer reefs around inhabited Pacific islands. We tested how local human impacts (low versus high determined using a threshold of 25 people km−2 reef) affected benthic community (i) structure, and (ii) relationships with environmental predictors using pre-defined models and model selection tools. Data on reef depth, benthic assemblages, and herbivorous fish communities were collected from field surveys. Additional data on thermal stress, storm exposure, and market gravity (a function of human population size and reef accessibility) were extracted from public repositories. Findings revealed that reefs subject to high local human impact were characterised by relatively more turf algae (>10% higher mean absolute coverage) and lower live coral cover (9% less mean absolute coverage) than reefs subject to low local human impact, but had similar macroalgal cover and coral morphological composition. Models based on spatio-physical predictors were significantly more accurate in explaining the variation of benthic assemblages at sites with low (mean adjusted-R2 = 0.35) rather than high local human impact, where relationships became much weaker (mean adjusted-R2 = 0.10). Model selection procedures also identified a distinct shift in the relative importance of different herbivorous fish functional groups in explaining benthic communities depending on the local human impact level. These results demonstrate that local human impacts alter natural systems and indicate that projecting climate change impacts may be particularly challenging at reefs close to higher human populations, where dependency and pressure on ecosystem services are highest.

Background There are limited treatment options for patients with metastatic or recurrent cervical cancer. Platinum-based chemotherapy plus the anti-vascular endothelial growth factor antibody bevacizumab remains the mainstay of advanced treatment. Pembrolizumab is Food and Drug Agency approved for programmed death ligand 1 (PD-L1) positive cervical cancer with a modest response rate. This is the first study to report the efficacy and safety of the PD-L1 antibody atezolizumab in combination with bevacizumab in advanced cervical cancer.Methods We report the results from a phase II, open-label, multicenter study (NCT02921269). Patients with advanced cervical cancer were treated with bevacizumab 15 mg/kg intravenous every 3 weeks and atezolizumab 1200 mg intravenous every 3 weeks. The primary objective was to measure the objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.Results In the total evaluable population (n=10), zero patients achieved an objective response as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) V.1.1, resulting in a confirmed ORR of 0%. Of note, there were two patients who achieved an unconfirmed PR. The DCR by RECIST V.1.1 was 60% (0% complete response, 0% partial response, 60% stable disease). Median PFS was 2.9 months (95% CI, 1.8 to 6) and median OS was 8.9 months (95% CI, 3.4 to 21.9). Safety results were generally consistent with the known safety profile of both drugs, notably with two high-grade neurologic events.Conclusions The combination of bevacizumab and atezolizumab did not meet the predefined efficacy endpoint, as addition of bevacizumab to PD-L1 blockade did not appear to enhance the ORR in cervical cancer.

Working memory is imprecise, and these imprecisions can be explained by the combined influences of random diffusive error and systematic drift toward a set of stable states ("attractors"). However, the neural correlates of diffusion and drift remain unknown. Here, we investigated how delay-period activity in frontal and parietal cortex, which is known to correlate with the decline in behavioral memory precision observed with increasing memory load, might relate to diffusion and drift. We analyzed data from an existing experiment in which subjects performed delayed recall for line orientation, at different loads, during functional magnetic resonance imaging (fMRI) scanning. To quantify the influence of drift and diffusion, we modeled subjects' behavior using a discrete attractor model and calculated within-subject correlation between frontal and parietal delay-period activity and whole-trial estimates of drift and diffusion. We found that although increases in frontal and parietal activity were associated with increases in both diffusion and drift, diffusion explained the most variance in frontal and parietal delay-period activity. In comparison, a subsequent whole-brain regression analysis showed that drift, rather than diffusion, explained the most variance in delay-period activity in lateral occipital cortex. These results are consistent with a model of the differential recruitment of general frontoparietal mechanisms in response to diffusive noise and of stimulus-specific biases in occipital cortex.

How does the neural representation of visual working memory content vary with behavioural priority? To address this, we recorded electroencephalography (EEG) while subjects performed a continuous-performance 2-back working memory task with oriented-grating stimuli. We tracked the transition of the neural representation of an item (n) from its initial encoding, to the status of ‘unprioritized memory item' (UMI), and back to ‘prioritized memory item', with multivariate inverted encoding modelling. Results showed that the representational format was remapped from its initially encoded format into a distinctive ‘opposite' representational format when it became a UMI and then mapped back into its initial format when subsequently prioritized in anticipation of its comparison with item n + 2. Thus, contrary to the default assumption that the activity representing an item in working memory might simply get weaker when it is deprioritized, it may be that a process of priority-based remapping helps to protect remembered information when it is not in the focus of attention.

ABSTRACT Antibiotics produced by bacteria play important roles in microbial interactions and competition Antibiosis can induce resistance mechanisms in target organisms, and at sublethal doses, antibiotics have been shown to globally alter gene expression patterns. Here, we show that hygromycin A from Streptomyces sp. strain 2AW. induces Chromobacterium violaceum ATCC 31532 to produce the purple antibiotic violacein. Sublethal doses of other antibiotics that similarly target the polypeptide elongation step of translation likewise induced violacein production, unlike antibiotics with different targets. C. violaceum biofilm formation and virulence against Drosophila melanogaster were also induced by translation-inhibiting antibiotics, and we identified an antibiotic-induced response (air) two-component regulatory system that is required for these responses. Genetic analyses indicated a connection between the Air system, quorum-dependent signaling, and the negative regulator VioS, leading us to propose a model for induction of violacein production. This work suggests a novel mechanism of interspecies interaction in which a bacterium produces an antibiotic in response to inhibition by another bacterium and supports the role of antibiotics as signal molecules. IMPORTANCE Secondary metabolites play important roles in microbial communities, but their natural functions are often unknown and may be more complex than appreciated. While compounds with antibiotic activity are often assumed to underlie microbial competition, they may alternatively act as signal molecules. In either scenario, microorganisms might evolve responses to sublethal concentrations of these metabolites, either to protect themselves from inhibition or to change certain behaviors in response to the local abundance of another species. Here, we report that violacein production by C. violaceum ATCC 31532 is induced in response to hygromycin A from Streptomyces sp. 2AW, and we show that this response is dependent on inhibition of translational polypeptide elongation and a previously uncharacterized two-component regulatory system. The breadth of the transcriptional response beyond violacein induction suggests a surprisingly complex metabolite-mediated microbe-microbe interaction and supports the hypothesis that antibiotics evolved as signal molecules. These novel insights will inform predictive models of soil community dynamics and the unintended effects of clinical antibiotic administration.

The HIV-1 reservoir consists of latently infected cells that persist despite antiretroviral therapy (ART). Elucidating the proviral genetic composition of the reservoir, particularly in the context of pre-therapy viral diversity, is therefore important to understanding reservoir formation and the persistence of latently infected cells. Here we investigate reservoir proviral variants from 13 Zambian acutely-infected individuals with additional pre-therapy sampling for a unique comparison to the ART-naïve quasispecies. We identified complete transmitted/founder (TF) viruses from seroconversion plasma samples, and additionally amplified and sequenced HIV-1 from plasma obtained one year post-infection and just prior to ART initiation. While the majority of proviral variants in the reservoir were most closely related to viral variants from the latest pre-therapy time point, we also identified reservoir proviral variants dating to or near the time of infection, and to intermediate time points between infection and treatment initiation. Reservoir proviral variants differing by five or fewer nucleotide changes from the TF virus persisted during treatment in five individuals, including proviral variants that exactly matched the TF in two individuals, one of whom had remained ART-naïve for more than six years. Proviral variants during treatment were significantly less divergent from the TF virus than plasma variants present at the last ART-naïve time point. These findings indicate that reservoir proviral variants are archived throughout infection, recapitulating much of the viral diversity that arises throughout untreated HIV-1 infection, and strategies to target and reduce the reservoir must therefore permit for the clearance of proviruses encompassing this extensive diversity.

Paternal cigarette smoke (CS) exposure is associated with increased risk of behavioral disorders and cancer in offspring, but the mechanism has not been identified. Here we use mouse models to investigate mechanisms and impacts of paternal CS exposure. We demonstrate that CS exposure induces sperm DNAme changes that are partially corrected within 28 days of removal from CS exposure. Additionally, paternal smoking is associated with changes in prefrontal cortex DNAme and gene expression patterns in offspring. Remarkably, the epigenetic and transcriptional effects of CS exposure that we observed in wild type mice are partially recapitulated in Nrf2-/- mice and their offspring, independent of smoking status. Nrf2 is a central regulator of antioxidant gene transcription, and mice lacking Nrf2 consequently display elevated oxidative stress, suggesting that oxidative stress may underlie CS-induced heritable epigenetic changes. Importantly, paternal sperm DNAme changes do not overlap with DNAme changes measured in offspring prefrontal cortex, indicating that the observed DNAme changes in sperm are not directly inherited. Additionally, the changes in sperm DNAme associated with CS exposure were not observed in sperm of unexposed offspring, suggesting the effects are likely not maintained across multiple generations.

We used functional magnetic resonance imaging (fMRI) to investigate the neural codes for representing stimulus information held in different states of priority in working memory. Human participants (male and female) performed delayed recall for 2 oriented gratings that could appear in any of several locations. Priority status was manipulated by a retrocue, such that one became the prioritized memory item (PMI) and another the unprioritized memory item (UMI). Using inverted encoding models (IEMs), we found that, in early visual cortex, the orientation of the UMI was represented in a neural representation that was rotated relative to the PMI. In intraparietal sulcus (IPS), we observed the analogous effect for the representation of the location of the UMI. Taken together, these results provide evidence for a common remapping mechanism that may be responsible for representing stimulus identity and stimulus context with different levels of priority in working memory.

SWI/SNF-family chromatin remodeling complexes, such as S. cerevisiae RSC, slide and eject nucleosomes to regulate transcription. Within nucleosomes, stiff DNA sequences confer spontaneous partial unwrapping, prompting whether and how SWI/SNF-family remodelers are specialized to remodel partially-unwrapped nucleosomes. RSC1 and RSC2 are orthologs of mammalian PBRM1 (polybromo) which define two separate RSC sub-complexes. Remarkably, in vitro the Rsc1-containing complex remodels partially-unwrapped nucleosomes much better than does the Rsc2-containing complex. Moreover, a rsc1Δ mutation, but not rsc2Δ, is lethal with histone mutations that confer partial unwrapping. Rsc1/2 isoforms both cooperate with the DNA-binding proteins Rsc3/30 and the HMG protein, Hmo1, to remodel partially-unwrapped nucleosomes, but show differential reliance on these factors. Notably, genetic impairment of these factors strongly reduces the expression of genes with wide nucleosome-deficient regions (e.g., ribosomal protein genes), known to harbor partially-unwrapped nucleosomes. Taken together, Rsc1/2 isoforms are specialized through composition and interactions to manage and remodel partially-unwrapped nucleosomes.

Knowing the difference between left and right is generally assumed throughout the brain MRI research community. However, we note widespread occurrences of left-right orientation errors in MRI open database repositories where volumes have contained systematic left-right flips between subject EPIs and anatomicals, due to having incorrect or missing file header information. Here we present a simple method in AFNI for determining the consistency of left and right within a pair of acquired volumes for a particular subject; the presence of EPI-anatomical inconsistency, for example, is a sign that dataset header information likely requires correction. The method contains both a quantitative evaluation as well as a visualizable verification. We test the functionality using publicly available datasets. Left-right flipping is not immediately obvious in most cases, so we also present visualization methods for looking at this problem (and other potential problems), using examples from both FMRI and DTI datasets.

Paragangliomas are rare neuroendocrine neoplasms derived from sympathetic or parasympathetic paraganglia and have the ability to secrete catecholamines. We present the case of a 37-year-old asymptomatic female who underwent right ovarian cystectomy for a mature cystic teratoma and was found to have an intra-tumoral paraganglioma. More research is needed to determine metastatic potential as well as the likelihood of recurrence of these unique neoplasms.

Despite the fact that multiple items can be held in working memory (WM), it is often the case that only one of these is relevant for guiding in-the-moment behavior. Therefore, understanding how priority is established and controlled in WM is an important problem. Data from Rose et al. (2016) have provided evidence that although neuroimaging evidence for an active trace of an “unprioritized memory item” (UMI) held in WM drops to baseline levels, evidence for its retention in WM can be “reactivated” by a single pulse of transcranial magnetic stimulation (TMS). Critically, this TMS-reactivation effect was specific to the first delay period of a dual serial retrocue (DSR) task, when the UMI could be needed for the trial’s second memory probe, and was not observed during the second delay period, when the uncued item was no longer needed (i.e., when it is an “irrelevant memory item” [IMI]). A problem for the interpretation of these results, however, is that the status of the UMI/IMI was confounded with time spent in WM, as well as with the number of intervening cognitive operations. Here, we report data from a follow-up study designed to replicate the findings Rose et al. (2016) and to add a condition that unconfounds time-since-sample-presentation and UMI/IMI status. The results indicate that the TMS-reactivation effect is, indeed, an index of status in WM (UMI vs. IMI), and not a mere consequence of time elapsed since sample presentation.

Background Coronary artery disease risk factors are associated with atrial fibrillation (AF) and coronary endothelial dysfunction (CED). We hypothesized that CED is associated with increased risk of incident AF among patients with chest pain and nonobstructive coronary artery disease. Methods and Results Three hundred patients with chest pain, nonobstructive coronary artery disease, and no history of AF underwent intracoronary acetylcholine infusion for evaluation of baseline epicardial (decrease in mid–left anterior descending coronary artery diameter in response to acetylcholine) and microvascular (34 mL/m2) left atrial volume index (odds ratio, 3.87; 95% CI, 1.60–9.11) were independent predictors of incident AF. Conclusions Patients with normal coronary endothelial function, as compared with those with CED and similar AF risk factors, have significantly lower incidence of AF on long‐term follow‐up. The potential mechanistic link between vascular dysfunction and AF development warrants further investigation.

We present the first case of traveler's diarrhea resulting in breast implant infection. An otherwise healthy 34-year-old female underwent breast augmentation. Five months later, while vacationing in Cancun, Mexico, she developed abdominal pain and diarrhea that progressed to include fevers and chills. Her symptoms persisted until she returned to the United States, at which point her primary care physician evaluated her on the fourth day of her illness. An abdominal CT scan was unremarkable; however, a complete metabolic panel demonstrated elevated transaminases. Her symptoms soon resolved without treatment. Fourteen days after symptom resolution, the patient developed right breast pain. She was evaluated in the surgical clinic where the breast was tender to palpation, swollen and without erythema. An ultrasound demonstrated a small amount of homogenous fluid surrounding the implant. She was prescribed amoxicillin–clavulanate 875–125 mg BID; however, she presented three days later with worsening pain, swelling and new erythema. She was taken to the operating room, where the abscess was incised, drained and the implant removed. Cultures grew Salmonella serogroup C. Patients should be counseled regarding the potential for hematogenous seeding of the breast cavity and implant following severe illness and bacteremia. It may be reasonable to provide patients with breast implants who are traveling to areas at high-risk for traveler's diarrhea or areas with limited medical resources with an antibiotic to take if moderate to severe symptoms of traveler's diarrhea were to develop while away. Keywords: Traveler's diarrhea, Salmonella, Breast, Infection, Implant

We present the first reported case of symptomatic hyponatremia after elective rhinoplasty. A 42-year old female underwent cosmetic rhinoplasty without complication and was discharged home after an uneventful recovery from general anesthesia. Just prior to midnight on the day of surgery, she reported nausea, which was treated with supportive care. Four hours later, she developed emesis, altered mental status, and seizure-like activity prompting medical transport to the emergency department. Upon arrival, she was hypotensive (BP 78/54), tachycardic (HR 112 bpm), hyponatremic (116 mmol/L), hypoosmotic (239 mOsm/kg), and had decreased consciousness (GCS = 10). She was admitted to the intensive care unit and had a central line placed for hypertonic saline infusion. Urinalysis was suggestive of SIADH (UrNa 111 mmol/L, UrOsm 546 mOsm/kg) and Nephrology was consulted. Her serum sodium was corrected over three days and her mental status improved. Surgeons should maintain a low threshold for further evaluation in patients who deviate from the expected postoperative recovery pathway. This report demonstrates that normal postoperative symptoms may mask underlying physiological abnormalities that can progress to acute life-threatening illness and underscores the importance of direct patient observation in the immediate postoperative period. Keywords: Rhinoplasty, SIADH, Hyponatremia, Complication

Abstract Background In an effort to reduce the increasing number of persons with mental illness (PMI) experiencing incarceration, co-responding police-mental health teams are being utilized as a way to divert PMI from the criminal justice system. Co-response teams are typically an inter-agency collaboration between police and mental health professionals, and in some cases include emergency medical personnel. These teams are intended to facilitate emergency response by linking patients to mental health resources rather than the criminal justice system, thus reducing burdens on both the criminal justice systems as well as local healthcare systems. The current study examines the barriers and facilitators of successfully implementing the Mobile Crisis Assistance Team model, a first-responder co-response team consisting of police officers, mental health professionals, and paramedics. Through content analysis of qualitative focus groups with team members and interviews with program stakeholders, this study expands previous findings by identifying additional professional cultural barriers and facilitators to program implementation while also exploring the role of clear, systematic policies and guidelines in program success. Results Findings demonstrate the value of having both flexible and formal policies and procedures to help guide program implementation; ample community resources and treatment services in order to successfully refer clients to needed services; and streamlined communication among participating agencies and the local healthcare community. A significant barrier to successful program implementation is that of role conflict and stigma. Indeed, members of the co-response teams experienced difficulty transitioning into their new roles and reported negative feedback from other first responders as well as from within their own agency. Initial agency collaboration, information sharing between agencies, and team building were also identified as facilitators to program implementation. Conclusion The current study provides a critical foundation for the implementation of first-responder police-mental health co-response teams. Cultural and systematic barriers to co-response team success should be understood prior to program creation and used to guide implementation. Furthermore, attention must be directed to cultivating community and professional support for co-response teams. Findings from this study can be used to guide future efforts to implement first-response co-response teams in order to positively engage PMI and divert PMI from the criminal justice system.

Abstract Background Team-based care has been identified as a key component in transforming primary care. An important factor in implementing team-based care is the requirement for teams to have daily huddles. During huddles, the care team, comprising physicians, nurses, and administrative staff, come together to discuss their daily schedules, track problems, and develop countermeasures to fix these problems. However, the impact of these huddles on staff burnout over time and patient outcomes are not clear. Further, there are challenges to implementing huddles in fast-paced primary care clinics. We will test whether the impact of a behavioral intervention of leadership training and problem-solving during the daily huddling process will result in higher consistent huddling in the intervention arm and result in higher team morale, reduced burnout, and improved patient outcomes. Methods/design We will conduct a care-team-level cluster randomized trial within primary care practices in two Midwestern states. The intervention will comprise a 1-day training retreat for leaders of primary care teams, biweekly sessions between huddle optimization coaches and members of the primary care teams, as well as coaching site visits at 30 and 100 days post intervention. This behavioral intervention will be compared to standard care, in which care teams have huddles without any support or training. Surveys of primary care team members will be administered at baseline (prior to training), 100 days (for the intervention arm only), and 180 days to assess team dynamics. The primary outcome of this trial will be team morale. Secondary outcomes will assess the impact of this intervention on clinician burnout, patient satisfaction, and quality of care. Discussion This trial will provide evidence on the impact of a behavioral intervention to implement huddles as a key component of team-based care models. Knowledge gained from this trial will be critical to broader deployment and successful implementation of team-based care models. Trial registration Clinicaltrials.gov, NCT03062670. Registered on 23 February 2017.

Febrile illnesses are among the most common reasons for visits to hospitals and clinics worldwide. Since fevers can arise from a wide range of diseases, identifying the causative pathogen is essential not only for effective personal treatment but also for early detection of outbreaks. The Defense Threat Reduction Agency (DTRA) tasked a coalition of commercial, academic, and government researchers with moving diagnostic technology concepts from ideation to field use as rapidly as possible using scientifically sound evaluations. DTRA's 24 Month Challenge program examined >30 technologies before fielding four technologies on four continents. >10,000 in field test results were recorded. Here we discuss our tiered evaluation system to assess candidate technologies developed by commercial partners and the process of field testing those technologies at various front-line clinics in Sierra Leone, Thailand, Peru, and Australia. We discuss successes and challenges for introducing two multiplexed lateral flow immunoassay (LFI) tests that detect malaria, dengue fever, melioidosis, and the plague. Additionally we discuss the use of a LFI reader that assisted the interpretation of the assay, communicated results to a data cloud, and greatly facilitated reach-back support. Lastly, we discuss the concurrent field testing of a multiplexed PCR assay on the FilmArray platform, which had an assay pouch specially designed for the 24 Month Challenge. Either standard-of-care or gold-standard testing were run alongside our fielded technologies to benchmark their performance. Keywords: Diagnostic device, Lateral flow immunoassay, Nested PCR, Field testing, Malaria, Dengue fever

Abstract Background Trichoderma fungi live in the soil rhizosphere and are beneficial for plant growth and pathogen resistance. Several species and strains are currently used worldwide in co-cultivation with crops as a biocontrol alternative to chemical pesticides even though little is known about the exact mechanisms of the beneficial interaction. We earlier found alamethicin, a peptide antibiotic secreted by Trichoderma, to efficiently permeabilise cultured tobacco cells. However, pre-treatment with Trichoderma cellulase made the cells resistant to subsequent alamethicin, suggesting a potential mechanism for plant tolerance to Trichoderma, needed for mutualistic symbiosis. Results We here investigated intact sterile-grown Arabidopsis thaliana seedlings germinated in water or growth medium. These could be permeabilised by alamethicin but not if pretreated with cellulase. By following the fluorescence from the membrane-impermeable DNA-binding probe propidium iodide, we found alamethicin to mainly permeabilise root tips, especially the apical meristem and epidermis cells, but not the root cap and basal meristem cells nor cortex cells. Alamethicin permeabilisation and cellulase-induced resistance were confirmed by developing a quantitative in situ assay based on NADP-isocitrate dehydrogenase accessibility. The combined assays also showed that hyperosmotic treatment after the cellulase pretreatment abolished the induced cellulase resistance. Conclusion We here conclude the presence of cell-specific alamethicin permeabilisation, and cellulase-induced resistance to it, in root tip apical meristem and epidermis of the model organism A. thaliana. We suggest that contact between the plasma membrane and the cell wall is needed for the resistance to remain. Our results indicate a potential mode for the plant to avoid negative effects of alamethicin on plant growth and localises the point of potential damage and response. The results also open up for identification of plant genetic components essential for beneficial effects from Trichoderma on plants.

Observing in six frequency bands from 27 to 280 GHz over a large sky area, the Simons Observatory (SO) is poised to address many questions in Galactic astrophysics in addition to its principal cosmological goals. In this work, we provide quantitative forecasts on astrophysical parameters of interest for a range of Galactic science cases. We find that SO can: constrain the frequency spectrum of polarized dust emission at a level of Δ β _d ≲ 0.01 and thus test models of dust composition that predict that β _d in polarization differs from that measured in total intensity; measure the correlation coefficient between polarized dust and synchrotron emission with a factor of two greater precision than current constraints; exclude the nonexistence of exo-Oort clouds at roughly 2.9 σ if the true fraction is similar to the detection rate of giant planets; map more than 850 molecular clouds with at least 50 independent polarization measurements at 1 pc resolution; detect or place upper limits on the polarization fractions of CO(2–1) emission and anomalous microwave emission at the 0.1% level in select regions; and measure the correlation coefficient between optical starlight polarization and microwave polarized dust emission in 1° patches for all lines of sight with N _H ≳ 2 × 10 ^20 cm ^−2 . The goals and forecasts outlined here provide a roadmap for other microwave polarization experiments to expand their scientific scope via Milky Way astrophysics. ^37

This article examines the prevalence of receiving course registration sanctions (i.e., past due balance notification, stop registration hold, and cancel registration order) caused by past due financial balances. The longitudinal data set follows all first-time, first-year students at a public flagship university during their first 2 years of college. We found that course registration sanctions were common at this university, as within the first 2 years of enrollment, 67% of students received a past due balance notification, 35% received a stop registration hold, and 11% received a cancel registration order. Differential patterns in the prevalence of course registration sanctions were evident across student demographic, academic, and financial factors. Specifically, students were significantly more likely to receive a registration sanction if they were: of high financial need, Black or African American, a first-generation college student, and had a lower ACT score. Furthermore, we found that Black and African American students were more likely to receive registration sanctions even after controlling for the size of the past due balance and their financial need. The findings provide evidence of systemic inequities that require institutional intervention.