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.

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.

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.

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.

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.

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.

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.

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.

Elevated Risk for Antimicrobial Drug-Resistant Shigella Infection among Men Who Have Sex with Men, United States, 2011-2015.

Shigella spp. cause ≈500,000 illnesses in the United States annually, and resistance to ciprofloxacin, ceftriaxone, and azithromycin is emerging. We investigated associations between transmission route and antimicrobial resistance among US shigellosis clusters reported during 2011-2015. Of 32 clusters, 9 were caused by shigellae resistant to ciprofloxacin (3 clusters), ceftriaxone (2 clusters), or azithromycin (7 clusters); 3 clusters were resistant to >1 of these drugs. We observed resistance to any of these drugs in all 7 clusters among men who have sex with men (MSM) but in only 2 of the other 25 clusters (p<0.001). Azithromycin resistance was more common among MSM-associated clusters than other clusters (86% vs. 4% of clusters; p<0.001). For adults with suspected shigellosis, clinicians should culture feces; obtain sex histories; discuss shigellosis prevention; and choose treatment, when needed, according to antimicrobial drug susceptibility. Public health interviews for enteric illnesses should encompass sex practices; health messaging for MSM must include shigellosis prevention.

Printed optics: phantoms for quantitative deep tissue fluorescence imaging: publisher's note.

This note points out a number of corrections that were omitted from the published version of the article [Opt. Lett.41, 5230 (2016)OPLEDP0146-959210.1364/OL.41.005230].

Printed optics: phantoms for quantitative deep tissue fluorescence imaging.

Three-dimensional (3D) printing allows for complex or physiologically realistic phantoms, useful, for example, in developing biomedical imaging methods and for calibrating measured data. However, available 3D printing materials provide a limited range of static optical properties. We overcome this limitation with a new method using stereolithography that allows tuning of the printed phantom's optical properties to match that of target tissues, accomplished by printing a mixture of polystyrene microspheres and clear photopolymer resin. We show that Mie theory can be used to design the optical properties, and demonstrate the method by fabricating a mouse phantom and imaging it using fluorescence optical diffusion tomography.

Notes from the Field: Shigellosis Outbreak Among Men Who Have Sex with Men and Homeless Persons - Oregon, 2015-2016.

In July 2015, Shigella sonnei infections with a specific pulsed-field gel electrophoresis (PFGE) pattern linked to a multistate outbreak were recognized among men who have sex with men (MSM) in the Portland metropolitan area, and an outbreak investigation was initiated. During November 2015, isolates with PFGE patterns indistinguishable from the outbreak strain were identified in cases reported in four women, none of whom had epidemiologic links to other affected persons; however, three reported homelessness. In the ensuing months, additional S. sonnei infections were reported among homeless persons in the Portland area.

Importation and domestic transmission of Shigella sonnei resistant to ciprofloxacin - United States, May 2014-February 2015.

In December 2014, PulseNet, the national molecular subtyping network for foodborne disease, detected a multistate cluster of Shigella sonnei infections with an uncommon pulsed-field gel electrophoresis (PFGE) pattern. CDC's National Antimicrobial Resistance Monitoring System (NARMS) laboratory determined that isolates from this cluster were resistant to ciprofloxacin, the antimicrobial medication recommended to treat adults with shigellosis. To understand the scope of the outbreak and to try to identify its source, CDC and state and local health departments conducted epidemiologic and laboratory investigations. During May 2014-February 2015, PulseNet identified 157 cases in 32 states and Puerto Rico; approximately half were associated with international travel. Nine of the cases identified by PulseNet, and another 86 cases without PFGE data, were part of a related outbreak of ciprofloxacin-resistant shigellosis in San Francisco, California. Of 126 total isolates with antimicrobial susceptibility information, 109 (87%) were nonsusceptible to ciprofloxacin (108 were resistant, and one had intermediate susceptibility). Travelers need to be aware of the risks of acquiring multidrug-resistant pathogens, carefully wash their hands, and adhere to food and water precautions during international travel. Clinicians should request stool cultures and antimicrobial susceptibilities when they suspect shigellosis, and counsel shigellosis patients to follow meticulous hygiene regimens while ill.

Notes from the Field: Outbreaks of Shigella sonnei Infection with Decreased Susceptibility to Azithromycin Among Men Who Have Sex with Men - Chicago and Metropolitan Minneapolis-St. Paul, 2014.

Increasing rates of shigellosis among adult males, particularly men who have sex with men (MSM), have been documented in the United States, Canada, and Europe, and MSM appear to be at greater risk for infection with shigellae that are not susceptible to ciprofloxacin or azithromycin. Azithromycin is the first-line empiric antimicrobial treatment for shigellosis among children and is a second-line treatment among adults. Isolates collected in 2014 in two U.S. cities from outbreaks of shigellosis displayed highly similar pulsed-field gel electrophoresis (PFGE) patterns and decreased susceptibility to azithromycin (DSA). This report summarizes and compares the findings from investigations of the two outbreaks, which occurred among MSM in metropolitan Minneapolis-St. Paul, Minnesota, and Chicago, Illinois.

Notes from the field: outbreak of diarrheal illness caused by Shigella flexneri - American Samoa, May-June 2014.

On May 9, 2014, a physician at hospital A in American Samoa noticed an abnormally high number of children presenting to the emergency department with bloody diarrhea. Based on preliminary testing of stool specimens, Entamoeba histolytica infection was suspected as a possible cause. Shigella was also suspected in a subset of samples. On May 22, the American Samoa Department of Health requested assistance from CDC with the outbreak investigation. The goals of the investigation were to establish the presence of an outbreak, characterize its epidemiology and etiology, and recommend control measures. The CDC field team reviewed the emergency department log book for cases of diarrheal illness during April 15-June 13, 2014. During this period, 280 cases of diarrheal illness were recorded, with a peak occurring on May 10. Twice as many cases occurred during this period in 2014 compared with the same period in 2011, the most recent year for which comparable surveillance data were available. Cases were widely distributed across the island. The highest number of cases occurred in children aged 0-9 years. Across age groups, cases were similarly distributed among males and females. These patterns are not consistent with the epidemiology of disease caused by E. histolytica, which tends to cause more cases in males of all ages.

Incidence of Cronobacter spp. infections, United States, 2003-2009.

During 2003-2009, we identified 544 cases of Cronobacter spp. infection from 6 US states. The highest percentage of invasive infections occurred among children <5 years of age; urine isolates predominated among adults. Rates of invasive infections among infants approximate earlier estimates. Overall incidence of 0.66 cases/100,000 population was higher than anticipated.

Notes from the field: Shigella with decreased susceptibility to azithromycin among men who have sex with men - United States, 2002-2013.

Bacteria of the genus Shigella cause approximately 500,000 illnesses each year in the United States. Diarrhea (sometimes bloody), fever, and stomach cramps typically start 1-2 days after exposure and usually resolve in 5-7 days. For patients with severe disease, bloody diarrhea, or compromised immune systems, antibiotic treatment is recommended, but resistance to traditional first-line antibiotics (e.g., ampicillin and trimethoprim-sulfamethoxazole) is common. For multidrugresistant cases, azithromycin, the most frequently prescribed antibiotic in the United States, is recommended for both children and adults. However, not all Shigellae are susceptible to azithromycin. Nonsusceptible isolates exist but are not usually identified because there are no clinical laboratory guidelines for azithromycin susceptibility testing. However, to monitor susceptibility of Shigellae in the United States, CDC's National Antimicrobial Resistance Monitoring System (NARMS) has, since 2011, routinely measured the azithromycin minimum inhibitory concentration (MIC) for every 20th Shigella isolate submitted from public health laboratories to CDC, as well as outbreak-associated isolates. All known U.S. Shigella isolates with decreased susceptibility to azithromycin (DSA-Shigella), and the illnesses caused by them, are described in this report.

Dynamics of shigellosis epidemics: estimating individual-level transmission and reporting rates from national epidemiologic data sets.

Shigellosis, a diarrheal disease, is endemic worldwide and is responsible for approximately 15,000 laboratory-confirmed cases in the United States every year. However, patients with shigellosis often do not seek medical care. To estimate the burden of shigellosis, we extended time-series susceptible-infected-recovered models to infer epidemiologic parameters from underreported case data. We applied the time-series susceptible-infected-recovered-based inference schemes to analyze the largest surveillance data set of Shigella sonnei in the United States from 1967 to 2007 with county-level resolution. The dynamics of shigellosis transmission show strong annual and multiyear cycles, as well as seasonality. By using the schemes, we inferred individual-level parameters of shigellosis infection, including seasonal transmissibilities and basic reproductive number (R0). In addition, this study provides quantitative estimates of the reporting rate, suggesting that the shigellosis burden in the United States may be more than 10 times the number of laboratory-confirmed cases. Although the estimated reporting rate is generally under 20%, and R0 is generally under 1.5, there is a strong negative correlation between estimates of the reporting rate and R0. Such negative correlations are likely to pose identifiability problems in underreported diseases. We discuss complementary approaches that might further disentangle the true reporting rate and R0.

Sustained improvements in handwashing indicators more than 5 years after a cluster-randomised, community-based trial of handwashing promotion in Karachi, Pakistan.

OBJECTIVE: To evaluate handwashing behaviour 5 years after a handwashing intervention in Karachi, Pakistan. METHODS: In 2003, we randomised neighbourhoods to control, handwashing promotion, or handwashing promotion and water treatment. Intervention households were given soap +/- water treatment product and weekly handwashing education for 9 months. In 2009, we re-enrolled 461 households from the three study groups: control (160), handwashing (141), and handwashing + water treatment (160) and assessed hygiene-related outcomes, accounting for clustering. RESULTS: Intervention households were 3.4 times more likely than controls to have soap at their handwashing stations during the study visit [293/301 (97%) vs. 45/159 (28%), P < 0.0001]. While nearly all households reported handwashing after toileting, intervention households more commonly reported handwashing before cooking [relative risk (RR) 1.2 (95% confidence interval (CI) 1.0-1.4)] and before meals [RR 1.7 (95% CI, 1.3-2.1)]. Control households cited a mean of 3.87 occasions for washing hands; handwashing households, 4.74 occasions; and handwashing + water treatment households, 4.78 occasions (P < 0.0001). Households reported purchasing a mean of 0.65 (control), 0.91 (handwashing) and 1.1 (handwashing + water treatment) bars of soap/person/month (P < 0.0001). CONCLUSIONS: Five years after receiving handwashing promotion, intervention households were more likely to have soap at the household handwashing station, know key times to wash hands and report purchasing more soap than controls, suggesting habituation of improved handwashing practices in this population. Intensive handwashing promotion may be an effective strategy for habituating hygiene behaviours and improving health.