A stable, distributed code for cue value in mouse cortex during reward learning.

The ability to associate reward-predicting stimuli with adaptive behavior is frequently attributed to the prefrontal cortex, but the stimulus-specificity, spatial distribution, and stability of prefrontal cue-reward associations are unresolved. We trained head-fixed mice on an olfactory Pavlovian conditioning task and measured the coding properties of individual neurons across space (prefrontal, olfactory, and motor cortices) and time (multiple days). Neurons encoding cues or licks were most common in the olfactory and motor cortex, respectively. By quantifying the responses of cue-encoding neurons to six cues with varying probabilities of reward, we unexpectedly found value coding in all regions we sampled, with some enrichment in the prefrontal cortex. We further found that prefrontal cue and lick codes were preserved across days. Our results demonstrate that individual prefrontal neurons stably encode components of cue-reward learning within a larger spatial gradient of coding properties.

Parabrachial tachykinin1-expressing neurons involved in state-dependent breathing control.

Breathing is regulated automatically by neural circuits in the medulla to maintain homeostasis, but breathing is also modified by behavior and emotion. Mice have rapid breathing patterns that are unique to the awake state and distinct from those driven by automatic reflexes. Activation of medullary neurons that control automatic breathing does not reproduce these rapid breathing patterns. By manipulating transcriptionally defined neurons in the parabrachial nucleus, we identify a subset of neurons that express the Tac1, but not Calca, gene that exerts potent and precise conditional control of breathing in the awake, but not anesthetized, state via projections to the ventral intermediate reticular zone of the medulla. Activating these neurons drives breathing to frequencies that match the physiological maximum through mechanisms that differ from those that underlie the automatic control of breathing. We postulate that this circuit is important for the integration of breathing with state-dependent behaviors and emotions.

Topographic representation of current and future threats in the mouse nociceptive amygdala.

Adaptive behaviors arise from an integration of current sensory context and internal representations of past experiences. The central amygdala (CeA) is positioned as a key integrator of cognitive and affective signals, yet it remains unknown whether individual populations simultaneously carry current- and future-state representations. We find that a primary nociceptive population within the CeA of mice, defined by CGRP-receptor (Calcrl) expression, receives topographic sensory information, with spatially defined representations of internal and external stimuli. While Calcrl+ neurons in both the rostral and caudal CeA respond to noxious stimuli, rostral neurons promote locomotor responses to externally sourced threats, while caudal CeA Calcrl+ neurons are activated by internal threats and promote passive coping behaviors and associative valence coding. During associative fear learning, rostral CeA Calcrl+ neurons stably encode noxious stimulus occurrence, while caudal CeA Calcrl+ neurons acquire predictive responses. This arrangement supports valence-aligned representations of current and future threats for the generation of adaptive behaviors.

"At Least Somebody Sees You as a Hero": Fatherhood Stress and Well-Being in Ghana.

Fathers' mental health and behaviors influence child development and partner well-being, yet paternal stress and well-being are frequently overlooked; especially in non-Western settings. The aim of this mixed-methods study was to quantitatively assess the impact of parenting stress on fathers' overall well-being in Ghana, West Africa; while qualitatively delving into their lived experiences as fathers. We used a qual/quant mixed-methods approach in this study. The study was conducted in three distinct locations in Ghana (a) Ada, a rural community on the Southeastern coast; (b) Kumasi, an urban setting in upper Southern Ghana; and (c) Sunyani, a peri-urban setting in West-central Ghana. Paternal stress was measured with the Aggravation in Parenting Scale (APS) and well-being was assessed using the Secure Flourishing Index (SFI). Textual data from focus group interviews were sorted using inductive coding and aggregated into overarching themes. Thirty-eight Ghanaian fathers ages 21 to 74 years participated in the study, average age 43 (±12.12 SD), median 39.5. Correlation analyses showed a strong, negative association between paternal stress and well-being (R = -0.63; p < .0001), which was supported in linear regression models (ß = -1.04; 95% CI: -1.62, -0.45; p<.0001). Emergent themes of fatherhood stress included financial (employment, food, education, and health care), social (norms and expectations), and psychological (mental work, discipline, relationships, and coping strategies) stressors. A fourth overarching theme of pride and joy in parenting permeated the interviews. Ghanaian fathers with higher parenting stress experience lower overall well-being. Identified stressors could guide interventions that bolster the well-being of fathers and their families.

Preferences for Shigellosis-Related Health Promotion Materials for Gay, Bisexual, and Other Men Who Have Sex With Men: Results From a Qualitative Assessment, Atlanta, GA.

BACKGROUND: Shigellosis, an acute diarrheal disease, is the third most common bacterial infection in the United States. Shigellosis most commonly affects children younger than 5 years; however, clusters and outbreaks of shigellosis have been reported among gay, bisexual, and other men who have sex with men (MSM). Evidence suggests that knowledge of shigellosis among MSM is low, indicating health promotion outreach is needed for this population. METHODS: To inform the development of shigellosis-related health communication materials and strategies, 6 focus groups were conducted in 2017, in Atlanta, GA among 24 self-identified gay and bisexual men. Participants were asked about their preferences and recommendations for health communication materials. RESULTS: Participants indicated they would prefer a range of physical and virtual materials placed in diverse locations where the community would see them. Respondents recommended health messages be simple, quick to read, and concise with limited word counts. Participants also advised the use of diverse images that were inclusive of couples of varying sexual orientations to reduce stigma. Participants advocated for the use of humor and provocative images to increase user engagement. CONCLUSIONS: The results emphasize the potential benefits of conducting formative research when designing health communication materials. Incorporating messaging preferences of MSM in the development of shigellosis-related health communication materials could enhance their relevance for the target population while also avoiding unintended consequences associated with stigmatizing MSM.

Demographic and Clinical Factors Associated With Death Among Persons <21 Years Old With Multisystem Inflammatory Syndrome in Children-United States, February 2020-March 2021.

Multisystem inflammatory syndrome in children (MIS-C) occurs among persons aged <21 years following severe acute respiratory syndrome coronavirus 2 infection. Among 2818 MIS-C cases, 35 (1.2%) deaths were reported, primarily affecting racial/ethnic minority persons. Being 16-20 years old or having comorbidities was associated with death. Targeting coronavirus disease 2019 prevention among these groups and their caregivers might prevent MIS-C-related deaths.

Temperature, topography, soil characteristics, and NDVI drive habitat preferences of a shade-tolerant invasive grass.

AIM: Despite the large literature documenting the negative effects of invasive grasses, we lack an understanding of the drivers of their habitat suitability, especially for shade-tolerant species that do not respond positively to canopy disturbance. We aimed to understand the environmental niche and potential spatial distribution of a relatively new invasive species, wavyleaf basketgrass (Oplismenus undulatifolius (Ard.) Roem. & Schult, WLBG) by leveraging data available at two different spatial scales. LOCATION: Mid-Atlantic region of the United States. METHODS: Maximum entropy modeling (Maxent) was used to predict the habitat suitability of WLBG at the regional scale and the landscape scale. Following variable evaluation, model calibration, and model evaluation, final models were created using 1,000 replicates and projected to each study area. RESULTS: At the regional scale, our best models show that suitability for WLBG was driven by relatively high annual mean temperatures, low temperature seasonality and monthly range, low slope, and high cumulative Normalized Difference Vegetation Index (NDVI). At the landscape scale, suitability was highest near roads and streams, far from trails, at low elevations, in sandy, moist soil, and in areas with high NDVI. MAIN CONCLUSIONS: We found that invasion potential of this relatively new invader appears high in productive, mesic habitats at low slope and elevations. At the regional scale, our model predicted areas of suitable habitat far outside areas where WLBG has been reported, including large portions of Virginia and West Virginia, suggests serious potential for spread. However, large portions of this area carry a high extrapolation risk and should therefore be interpreted with caution. In contrast, at the landscape level, the suitability of WLBG is largely restricted to areas near current presence points, suggesting that the expansion risk of this species within Shenandoah National Park is somewhat limited.

Chronic Gq signaling in AgRP neurons does not cause obesity.

Maintaining energy homeostasis requires coordinating physiology and behavior both on an acute timescale to adapt to rapid fluctuations in caloric intake and on a chronic timescale to regulate body composition. Hypothalamic agouti-related peptide (AgRP)-expressing neurons are acutely activated by caloric need, and this acute activation promotes increased food intake and decreased energy expenditure. On a longer timescale, AgRP neurons exhibit chronic hyperactivity under conditions of obesity and high dietary fat consumption, likely due to leptin resistance; however, the behavioral and metabolic effects of chronic AgRP neuronal hyperactivity remain unexplored. Here, we use chemogenetics to manipulate Gq signaling in AgRP neurons in mice to explore the hypothesis that chronic activation of AgRP neurons promotes obesity. Inducing chronic Gq signaling in AgRP neurons initially increased food intake and caused dramatic weight gain, in agreement with published data; however, food intake returned to baseline levels within 1 wk, and body weight returned to baseline levels within 60 d. Additionally, we found that, when mice had elevated body weight due to chronic Gq signaling in AgRP neurons, energy expenditure was not altered but adiposity and lipid metabolism were both increased, even under caloric restriction. These findings reveal that the metabolic and behavioral effects of chronic Gq signaling in AgRP neurons are distinct from the previously reported effects of acute Gq signaling and also of leptin insensitivity.

Dissociable control of unconditioned responses and associative fear learning by parabrachial CGRP neurons.

Parabrachial CGRP neurons receive diverse threat-related signals and contribute to multiple phases of adaptive threat responses in mice, with their inactivation attenuating both unconditioned behavioral responses to somatic pain and fear-memory formation. Because CGRPPBN neurons respond broadly to multi-modal threats, it remains unknown how these distinct adaptive processes are individually engaged. We show that while three partially separable subsets of CGRPPBN neurons broadly collateralize to their respective downstream partners, individual projections accomplish distinct functions: hypothalamic and extended amygdalar projections elicit assorted unconditioned threat responses including autonomic arousal, anxiety, and freezing behavior, while thalamic and basal forebrain projections generate freezing behavior and, unexpectedly, contribute to associative fear learning. Moreover, the unconditioned responses generated by individual projections are complementary, with simultaneous activation of multiple sites driving profound freezing behavior and bradycardia that are not elicited by any individual projection. This semi-parallel, scalable connectivity schema likely contributes to flexible control of threat responses in unpredictable environments.

Shigellosis Among Gay and Bisexual Men: A Qualitative Assessment to Examine Knowledge, Attitudes, and Practices.

BACKGROUND: Shigellosis is a highly contagious enteric bacterial disease transmitted through the fecal-oral route. It is primarily transmitted through person-to-person contact and via contaminated food and water. Outbreaks of shigellosis among men who have sex with men (MSM) attributed to sexual person-to-person contact have been reported. These outbreaks are of concern because they are often caused by multidrug-resistant strains of Shigella. Little is known about shigellosis-related knowledge, attitudes, and practices among gay, bisexual, and other MSM. METHODS: Six focus groups were conducted among self-identified gay or bisexual men in Atlanta, GA, in Fall 2017. Participants were asked about shigellosis-related knowledge, attitudes, and practices. Focus groups were audio recorded, and the transcribed audio was analyzed using inductive and deductive thematic coding. RESULTS: Among the 24 focus group participants, most perceived that diarrheal illness was caused by contaminated food. Knowledge of shigellosis and Shigella was low, with most never having heard of the disease or bacteria. Participants did not perceive shigellosis to be a serious health concern, especially when compared with HIV; however, they did perceive gay and bisexual men to be at risk of Shigella infection. Participants reported mixed intentions to change sexual behaviors to prevent shigellosis or talk with sexual partners about diarrhea. CONCLUSIONS: Health communication and education efforts could be used to increase knowledge about shigellosis and shift perceptions about the severity of shigellosis among gay, bisexual, and other MSM. Additional work is needed to identify effective ways to promote shigellosis-related prevention behaviors among gay, bisexual, and other MSM.

Decreased Susceptibility to Azithromycin in Clinical Shigella Isolates Associated with HIV and Sexually Transmitted Bacterial Diseases, Minnesota, USA, 2012-2015.

Shigellosis outbreaks caused by Shigella with decreased susceptibility to azithromycin (DSA-Shigella) among men who have sex with men (MSM) have been reported worldwide. We describe sexual health indicators and antimicrobial drug resistance for shigellosis cases in Minnesota, USA. We analyzed a sample of isolates received during 2012-2015 and cross-referenced cases with the Minnesota Department of Health Sexually Transmitted Disease Database to ascertain patients' HIV status and recent chlamydia, gonorrhea, and syphilis infections. Of 691 Shigella isolates, 46 (7%) were DSA-Shigella; 91% of DSA-Shigella patients were men, of whom 60% were living with HIV. Among men, those with DSA-Shigella infection had greater odds of living with HIV, identifying as MSM, or having a recent diagnosis of a sexually transmitted disease. DSA-Shigella was associated with MSM, HIV infection, and recent sexually transmitted disease. To decrease spread of DSA-Shigella, interventions targeted at communities at high risk are needed.

Identification and characterization of Shigella with decreased susceptibility to azithromycin in the United States, 2005 to 2014.

OBJECTIVES: Our objectives were to identify Shigella isolates in the United States with decreased susceptibility to azithromycin (DSA) and characterize the genetic mechanisms responsible for this resistance. METHODS: The National Antimicrobial Resistance Monitoring System (NARMS) at the US Centers for Disease Control and Prevention (CDC) collects and conducts broth microdilution antimicrobial susceptibility testing on Shigella to determine minimum inhibitory concentrations (MICs) for up to 15 drugs, including azithromycin. Isolates with decreased susceptibility to azithromycin were subjected to molecular methods (e.g., polymerase chain reaction [PCR], whole-genome sequencing, and plasmid typing/transformation) to identify the genetic mechanisms of resistance. RESULTS: A total of 118 isolates with decreased susceptibility to azithromycin were tested-65 (55%) isolates contained only mphA, 1 (<1%) isolate contained only ermB, and 51 (43%) isolates contained both mechanisms. Seven isolates contained IncFII plasmids with mphA, ermB, or mphA and ermB, whereas one isolate contained an IncB/O plasmid with mphA. One (<1%) isolate that contained neither mphA nor ermB contained mutations in rrlH, rplD, and rplV genes and an insertion in rplV, the functions of which are not yet known. CONCLUSION: Additional studies are needed to understand the effect on treatment outcomes, epidemiology and possible additional mechanisms responsible for the decreased susceptibility of azithromycin in Shigella.

Quinolone nonsusceptibility among enteric pathogens isolated from international travelers - Foodborne Diseases Active Surveillance Network (FoodNet) and National Antimicrobial Monitoring System (NARMS), 10 United States sites, 2004 - 2014.

Gastrointestinal illnesses are the most frequently diagnosed conditions among returning U.S. travelers. Although most episodes of travelers' diarrhea do not require antibiotic therapy, fluoroquinolones (a type of quinolone antibiotic) are recommended for treatment of moderate and severe travelers' diarrhea as well as many other types of severe infection. To assess associations between quinolone susceptibility and international travel, we linked data about isolate susceptibility in NARMS to cases of enteric infections reported to FoodNet. We categorized isolates as quinolone-nonsusceptible (QNS) if they were resistant or had intermediate susceptibility to ≥1 quinolone. Among 1,726 travel-associated infections reported to FoodNet with antimicrobial susceptibility data in NARMS during 2004-2014, 56% of isolates were quinolone-nonsusceptible, of which most (904/960) were Campylobacter. International travel was associated with >10-fold increased odds of infection with quinolone-nonsusceptible bacteria. Most QNS infections were associated with travel to Latin America and the Caribbean (390/743; 52%); however, the greatest risk of QNS infection was associated with travel to Africa (120 per 1,000,000 passenger journeys). Preventing acquisition and onward transmission of antimicrobial-resistant enteric infections among travelers is critical.

Parabrachial Complex: A Hub for Pain and Aversion.

The parabrachial nucleus (PBN) has long been recognized as a sensory relay receiving an array of interoceptive and exteroceptive inputs relevant to taste and ingestive behavior, pain, and multiple aspects of autonomic control, including respiration, blood pressure, water balance, and thermoregulation. Outputs are known to be similarly widespread and complex. How sensory information is handled in PBN and used to inform different outputs to maintain homeostasis and promote survival is only now being elucidated. With a focus on taste and ingestive behaviors, pain, and thermoregulation, this review is intended to provide a context for analysis of PBN circuits involved in aversion and avoidance, and consider how information of various modalities, interoceptive and exteroceptive, is processed within PBN and transmitted to distinct targets to signal challenge, and to engage appropriate behavioral and physiological responses to maintain homeostasis.

Effect of Bismuth Subsalicylate vs Placebo on Use of Antibiotics Among Adult Outpatients With Diarrhea in Pakistan: A Randomized Clinical Trial.

Importance: Many of the 4.5 billion annual episodes of diarrhea are treated unnecessarily with antibiotics; prevalence of antibiotic resistance among diarrheal pathogens is increasing. Knowledge-based antibiotic stewardship interventions typically yield little change in antibiotic use. Objective: To compare antibiotic use among adult outpatients with diarrhea given bismuth subsalicylate (BSS) or placebo. Design, Setting, and Participants: This randomized clinical trial took place from April to October 2014. Participants were patients aged 15 to 65 years with acute, nonbloody diarrhea from 22 outpatient clinics in Karachi, Pakistan. Participants were interviewed about symptoms and health care utilization during the 5 days after enrollment. Group assignment was concealed from participants, field staff, and the statistician. Primary analysis occurred from August to September 2015. Interventions: Participants were randomly assigned (1:1) to receive BSS or placebo for 48 hours or less. Main Outcomes and Measures: Use of systemic antibiotics within 5 days of enrollment. Secondary outcomes included measures of duration and severity of illness. Results: Among eligible patients, 39 declined to participate, 440 enrolled, and 1 enrolled participant was lost to follow-up, for a total of 439 patients included in the analysis. Median (interquartile range) participant age was 32 (23-45) years and 187 (43%) were male. Two hundred twenty patients were randomized to BSS and 220 were randomized to placebo. Overall, 54 participants (12%) used systemic antibiotics (16% in the placebo group and 9% in the BSS group); all antibiotic use followed consultation with a physician. Use of any antibiotic was significantly lower in the BSS group (20 of 220 vs 34 of 219 patients; odds ratio [OR], 0.54; 95% CI, 0.30-0.98), as was use of fluoroquinolones (8 of 220 vs 20 of 219 patients; OR, 0.38; 95% CI, 0.16-0.88). Rates of care seeking and hospitalization were similar between groups and no difference was detected in timing of diarrhea resolution. However, those in the BSS group less commonly received intravenous rehydration (14 of 220 vs 27 of 219 patients; OR, 0.48; 95% CI, 0.25-0.95) and missed less work (median [interquartile range], 0 [0-1] vs 1 [0-1] day; P = .04) during follow-up. Conclusions and Relevance: This study found less antibiotic use among participants given BSS for acute diarrhea in a setting where antibiotics are commonly used to treat diarrhea. Encouraging health care professionals in such settings to recommend BSS as frontline treatment for adults with diarrhea, and promoting BSS for diarrhea self-management, may reduce antibiotic use and rates of antibiotic resistance globally. Trial Registration: ClinicalTrials.gov identifier: NCT02047162.

Evaluation of the impact of shigellosis exclusion policies in childcare settings upon detection of a shigellosis outbreak.

BACKGROUND: In the event of a shigellosis outbreak in a childcare setting, exclusion policies are typically applied to afflicted children to limit shigellosis transmission. However, there is scarce evidence of their impact. METHODS: We evaluated five exclusion policies: Children return to childcare after: i) two consecutive laboratory tests (either PCR or culture) do not detect Shigella, ii) a single negative laboratory test (PCR or culture) does not detect Shigella, iii) seven days after beginning antimicrobial treatment, iv) after being symptom-free for 24 h, or v) 14 days after symptom onset. We also included four treatments to assess the policy options: i) immediate, effective treatment; ii) effective treatment after laboratory diagnosis; iii) no treatment; iv) ineffective treatment. Relying on published data, we calculated the likelihood that a child reentering childcare would be infectious, and the number of childcare-days lost per policy. RESULTS: Requiring two consecutive negative PCR tests yielded a probability of onward transmission of < 1%, with up to 17 childcare-days lost for children receiving effective treatment, and 53 days lost for those receiving ineffective treatment. CONCLUSIONS: Of the policies analyzed, requiring negative PCR testing before returning to childcare was the most effective to reduce the risk of shigellosis transmission, with one PCR test being the most effective for the least childcare-days lost.

Encoding of danger by parabrachial CGRP neurons.

Animals must respond to various threats to survive. Neurons that express calcitonin gene-related peptide in the parabrachial nucleus (CGRPPBN neurons) relay sensory signals that contribute to satiation and pain-induced fear behaviour, but it is unclear how they encode these distinct processes. Here, by recording calcium transients in vivo from individual neurons in mice, we show that most CGRPPBN neurons are activated by noxious cutaneous (shock, heat, itch) and visceral stimuli (lipopolysaccharide). The same neurons are inhibited during feeding, but become activated during satiation, consistent with evidence that CGRPPBN neurons prevent overeating. CGRPPBN neurons are also activated during consumption of novel foods or by an auditory cue that has previously been paired with electrical footshocks. Correspondingly, silencing of CGRPPBN neurons attenuates the expression of food neophobia and conditioned fear responses. Therefore, in addition to transducing primary sensory danger signals, CGRPPBN neurons promote affective-behavioural states that limit harm in response to potential threats.

Disparities in severe shigellosis among adults - Foodborne diseases active surveillance network, 2002-2014.

BACKGROUND: Shigella causes approximately 500,000 illnesses, 6000 hospitalizations, and 40 deaths in the United States annually, but incidence and populations at risk for severe shigellosis among adults are unclear. This study describes severe shigellosis among US adults. METHODS: We analyzed Foodborne Diseases Active Surveillance Network data for infections caused by Shigella among adults ≥18 years old during 2002-2014. Criteria to define severe shigellosis included hospitalization, bacteremia, or death. We estimated annual incidence of shigellosis per 100,000 among adult populations, and conducted multivariable mixed-effects logistic regression to assess associations between severe shigellosis, demographic factors and Shigella species among adults with shigellosis. RESULTS: Among 9968 shigellosis cases, 2764 (28%) were severe. Restricting to cases due to S. sonnei and S. flexneri, median annual incidence of severe shigellosis among adults was 0.56 and highest overall incidence was among black males 18-49 years old (1.58). Among adults with shigellosis, odds of severe disease were higher among males than females aged 18-49 years old (OR [95% CI] = 1.32 [1.15-1.52], p < 0.001) and among males than females with S. flexneri infections (OR [95% CI] =1.39 [1.10-1.75], p = 0.005). The odds of severe shigellosis were higher among blacks than whites (OR [95% CI] = 1.36 [1.22-1.52], p < 0.001). CONCLUSIONS: Among adults, men 18-49 years old, particularly blacks, have the highest incidence of severe shigellosis. Among adults with shigellosis, severe shigellosis was associated with being male in age group 18-49 years, with infections caused by S. flexneri, and with black race. Future research should assess associations between severe shigellosis and sexual practices, antimicrobial resistance, comorbidities, and access to care.