Regional impact of multidrug-resistant organism prevention bundles implemented by facility type: A modeling study.

BACKGROUND: Emerging multidrug-resistant organisms (MDROs), such as carbapenem-resistant Enterobacterales (CRE), can spread rapidly in a region. Facilities that care for high-acuity patients with longer stays may have a disproportionate impact on this spread. OBJECTIVE: We assessed the impact of implementing preventive interventions, directed at a subset of facilities, on regional prevalence. METHODS: We developed a deterministic compartmental model, parametrized using CRE and patient transfer data. The model included the community and healthcare facilities within a US state. Individuals may be either susceptible or infectious with CRE. Individuals determined to be infectious through admission screening, periodic prevalence surveys (PPSs), or interfacility communication were placed in a state of lower transmissibility if enhanced infection prevention and control (IPC) practices were in place at a facility. RESULTS: Intervention bundles that included PPS and enhanced IPC practices at ventilator-capable skilled nursing facilities (vSNFs) and long-term acute-care hospitals (LTACHs) had the greatest impact on regional prevalence. The benefits of including targeted admission screening in acute-care hospitals, LTACHs, and vSNFs, and improved interfacility communication were more modest. Daily transmissions in each facility type were reduced following the implementation of interventions primarily focused at LTACHs and vSNFs. CONCLUSIONS: Our model suggests that interventions that include screening to limit unrecognized MDRO introduction to, or dispersal from, LTACHs and vSNFs slow regional spread. Interventions that pair detection and enhanced IPC practices within LTACHs and vSNFs may substantially reduce the regional burden.

Modelling counterfactual incidence during the transition towards culture-independent diagnostic testing.

BACKGROUND: Culture-independent diagnostic testing (CIDT) provides rapid results to clinicians and is quickly displacing traditional detection methods. Increased CIDT use and sensitivity likely result in higher case detection but might also obscure infection trends. Severe illness outcomes, such as hospitalization and death, are likely less affected by changes in testing practices and can be used as indicators of the expected case incidence trend had testing methods not changed. METHODS: Using US Foodborne Diseases Active Surveillance Network data during 1996-2019 and mixed effects quasi-Poisson regression, we estimated the expected yearly incidence for nine enteric pathogens. RESULTS: Removing the effect of CIDT use, CIDT panel testing and culture-confirmation of CIDT testing, the modelled incidence in all but three pathogens (Salmonella, Shigella, STEC O157) was significantly lower than the observed and the upward trend in Campylobacter was reversed from an observed 2.8% yearly increase to a modelled -2.8% yearly decrease (95% credible interval: -4.0, -1.4). CONCLUSIONS: Severe outcomes may be useful indicators in evaluating trends in surveillance systems that have undergone a marked change.

Public health impact of the U.S. Scenario Modeling Hub.

Beginning in December 2020, the COVID-19 Scenario Modeling Hub has provided quantitative scenario-based projections for cases, hospitalizations, and deaths, aggregated across up to nine modeling groups. Projections spanned multiple months into the future and provided timely information on potential impacts of epidemiological uncertainties and interventions. Projections results were shared with the public, public health partners, and the Centers for Disease Control COVID-19 Response Team. The projections provided insights on situational awareness and informed decision-making to mitigate COVID-19 disease burden (e.g., vaccination strategies). By aggregating projections from multiple modeling teams, the Scenario Modeling Hub provided rapidly synthesized information in times of great uncertainty and conveyed possible trajectories in the presence of emerging variants. Here we detail several use cases of these projections in public health practice and communication, including assessments of whether modeling results directly or indirectly informed public health communication or guidance. These include multiple examples where comparisons of projected COVID-19 disease outcomes under different vaccination scenarios were used to inform Advisory Committee for Immunization Practices recommendations. We also describe challenges and lessons learned during this highly beneficial collaboration.

Epidemiology and Antimicrobial Resistance of Campylobacter Infections in the United States, 2005-2018.

Background: Campylobacter is the most common cause of bacterial diarrhea in the United States; resistance to macrolides and fluoroquinolones limits treatment options. We examined the epidemiology of US Campylobacter infections and changes in resistance over time. Methods: The Foodborne Diseases Active Surveillance Network receives information on laboratory-confirmed Campylobacter cases from 10 US sites, and the National Antimicrobial Resistance Monitoring System receives a subset of isolates from these cases for antimicrobial susceptibility testing. We estimated trends in incidence of Campylobacter infection, adjusting for sex, age, and surveillance changes attributable to culture-independent diagnostic tests. We compared percentages of isolates resistant to erythromycin or ciprofloxacin during 2005-2016 with 2017-2018 and used multivariable logistic regression to examine the association of international travel with resistance. Results: Adjusted Campylobacter incidence remained stable or decreased for all groups analyzed since 2012. Among 2449 linked records in 2017-2018, the median patient age was 40.2 years (interquartile range, 21.6-57.8 years), 54.8% of patients were male, 17.2% were hospitalized, and 0.2% died. The percentage of resistant infections increased from 24.5% in 2005-2016 to 29.7% in 2017-2018 for ciprofloxacin (P < .001) and from 2.6% to 3.3% for erythromycin (P = .04). Persons with recent international travel had higher odds than nontravelers of having isolates resistant to ciprofloxacin (adjusted odds ratio [aOR] varied from 1.7 to 10.6 by race/ethnicity) and erythromycin (aOR = 1.7; 95% confidence interval, 1.3-2.1). Conclusions: Campylobacter incidence has remained stable or decreased, whereas resistance to antimicrobials recommended for treatment has increased. Recent international travel increased the risk of resistance.

Accounting for assay performance when estimating the temporal dynamics in SARS-CoV-2 seroprevalence in the U.S.

Reconstructing the incidence of SARS-CoV-2 infection is central to understanding the state of the pandemic. Seroprevalence studies are often used to assess cumulative infections as they can identify asymptomatic infection. Since July 2020, commercial laboratories have conducted nationwide serosurveys for the U.S. CDC. They employed three assays, with different sensitivities and specificities, potentially introducing biases in seroprevalence estimates. Using models, we show that accounting for assays explains some of the observed state-to-state variation in seroprevalence, and when integrating case and death surveillance data, we show that when using the Abbott assay, estimates of proportions infected can differ substantially from seroprevalence estimates. We also found that states with higher proportions infected (before or after vaccination) had lower vaccination coverages, a pattern corroborated using a separate dataset. Finally, to understand vaccination rates relative to the increase in cases, we estimated the proportions of the population that received a vaccine prior to infection.

Estimating the number of symptomatic SARS-CoV-2 infections among vaccinated individuals in the United States-January-July, 2021.

As of March 2021, three COVID-19 vaccines had been authorized by the U.S. Food and Drug Administration (FDA) for use in the United States. Each has substantial efficacy in preventing COVID-19. However, as efficacy from trials was <100% for all three vaccines, disease in vaccinated people is expected to occur. We created a spreadsheet-based tool to estimate the number of symptomatic COVID-19 cases among vaccinated people (vaccine breakthrough infections) based on published vaccine efficacy (VE) data, percent of the population that has been fully vaccinated, and average number of COVID-19 cases reported per day. We estimate that approximately 199,000 symptomatic vaccine breakthrough infections (95% CI: ~183,000-214,000 cases) occurred in the United States during January-July 2021 among >156 million fully vaccinated people. With high SARS-CoV-2 transmission and increasing numbers of people vaccinated in the United States, vaccine breakthrough infections will continue to accumulate. Understanding expectations regarding number of vaccine breakthrough infections enables accurate public health messaging to help ensure that the occurrence of such cases does not negatively affect vaccine perceptions, confidence, and uptake.

Estimating incidence of infection from diverse data sources: Zika virus in Puerto Rico, 2016.

Emerging epidemics are challenging to track. Only a subset of cases is recognized and reported, as seen with the Zika virus (ZIKV) epidemic where large proportions of infection were asymptomatic. However, multiple imperfect indicators of infection provide an opportunity to estimate the underlying incidence of infection. We developed a modeling approach that integrates a generic Time-series Susceptible-Infected-Recovered epidemic model with assumptions about reporting biases in a Bayesian framework and applied it to the 2016 Zika epidemic in Puerto Rico using three indicators: suspected arboviral cases, suspected Zika-associated Guillain-Barré Syndrome cases, and blood bank data. Using this combination of surveillance data, we estimated the peak of the epidemic occurred during the week of August 15, 2016 (the 33rd week of year), and 120 to 140 (50% credible interval [CrI], 95% CrI: 97 to 170) weekly infections per 10,000 population occurred at the peak. By the end of 2016, we estimated that approximately 890,000 (95% CrI: 660,000 to 1,100,000) individuals were infected in 2016 (26%, 95% CrI: 19% to 33%, of the population infected). Utilizing multiple indicators offers the opportunity for real-time and retrospective situational awareness to support epidemic preparedness and response.

Homelessness and Hepatitis A-San Diego County, 2016-2018.

BACKGROUND: Hepatitis A is a vaccine-preventable viral disease transmitted by the fecal-oral route. During 2016-2018, the County of San Diego investigated an outbreak of hepatitis A infections primarily among people experiencing homelessness (PEH) to identify risk factors and support control measures. At the time of the outbreak, homelessness was not recognized as an independent risk factor for the disease. METHODS: We tested the association between homelessness and infection with hepatitis A virus (HAV) using a test-negative study design comparing patients with laboratory-confirmed hepatitis A with control subjects who tested negative for HAV infection. We assessed risk factors for severe hepatitis A disease outcomes, including hospitalization and death, using multivariable logistic regression. We measured the frequency of indications for hepatitis A vaccination according to Advisory Committee on Immunization Practices (ACIP) guidelines. RESULTS: Among 589 outbreak-associated cases reported, 291 (49%) occurred among PEH. Compared with those who were not homeless, PEH had 3.3 (95% confidence interval [CI], 1.5-7.9) times higher odds of HAV infection, 2.5 (95% CI, 1.7-3.9) times higher odds of hospitalization, and 3.9 (95% CI, 1.1-16.9) times higher odds of death associated with hepatitis A. Among PEH, 212 (73%) patients recorded other ACIP indications for hepatitis A vaccination. CONCLUSIONS: PEH were at higher risk of infection with HAV and of severe hepatitis A disease outcomes compared with those not experiencing homelessness. Approximately one-fourth of PEH had no other ACIP indication for hepatitis A vaccination. These findings support the recent ACIP recommendation to add homelessness as an indication for hepatitis A vaccination.

Salmonella Serotypes: A Novel Measure of Association with Foodborne Transmission.

Most nontyphoidal Salmonella (NTS) illnesses in the United States are thought to be foodborne. However, transmission routes likely vary among the different serotypes. We developed a relative ranking of NTS serotypes according to the strength of their association with foodborne transmission. We used Laboratory-based Enteric Disease Surveillance data to estimate the proportion of infections for each Salmonella serotype reported from 1998 to 2015 and Foodborne Disease Outbreak Surveillance System data to calculate the proportion of foodborne outbreak-associated Salmonella illnesses caused by each serotype. We calculated the ratios of these proportions to create a foodborne relatedness (FBR) measure for each serotype. Of the top 20 serotypes, Saintpaul (2.14), Heidelberg (1.61), and Berta (1.48) had the highest FBR measures; Mississippi (0.01), Bareilly (0.13), and Paratyphi B variant L(+) tartrate(+) (0.20) had the lowest. The FBRs for the three most prevalent serotypes were 1.22 for Enteritidis, 0.77 for Typhimurium, and 1.16 for Newport. This method provides a quantitative approach to estimating the relative differences in the likelihood that an illness caused by a particular serotype was transmitted by food, which may aid in tailoring strategies to prevent Salmonella illnesses and guide future research into serotype-specific source attribution.

Differences Among Incidence Rates of Invasive Listeriosis in the U.S. FoodNet Population by Age, Sex, Race/Ethnicity, and Pregnancy Status, 2008-2016.

Listeria monocytogenes is a foodborne pathogen that disproportionally affects pregnant females, older adults, and immunocompromised individuals. Using U.S. Foodborne Diseases Active Surveillance Network (FoodNet) surveillance data, we examined listeriosis incidence rates and rate ratios (RRs) by age, sex, race/ethnicity, and pregnancy status across three periods from 2008 to 2016, as recent incidence trends in U.S. subgroups had not been evaluated. The invasive listeriosis annual incidence rate per 100,000 for 2008-2016 was 0.28 cases among the general population (excluding pregnant females), and 3.73 cases among pregnant females. For adults ≥70 years, the annual incidence rate per 100,000 was 1.33 cases. No significant change in estimated listeriosis incidence was found over the 2008-2016 period, except for a small, but significantly lower pregnancy-associated rate in 2011-2013 when compared with 2008-2010. Among the nonpregnancy-associated cases, RRs increased with age from 0.43 (95% confidence interval: 0.25-0.73) for 0- to 14-year olds to 44.9 (33.5-60.0) for ≥85-year olds, compared with 15- to 44-year olds. Males had an incidence of 1.28 (1.12-1.45) times that of females. Compared with non-Hispanic whites, the incidence was 1.57 (1.18-1.20) times higher among non-Hispanic Asians, 1.49 (1.22-1.83) among non-Hispanic blacks, and 1.73 (1.15-2.62) among Hispanics. Among females of childbearing age, non-Hispanic Asian females had 2.72 (1.51-4.89) and Hispanic females 3.13 (2.12-4.89) times higher incidence than non-Hispanic whites. We observed a higher percentage of deaths among older patient groups compared with 15- to 44-year olds. This study is the first characterizing higher RRs for listeriosis in the United States among non-Hispanic blacks and Asians compared with non-Hispanic whites. This information for public health risk managers may spur further research to understand if differences in listeriosis rates relate to differences in consumption patterns of foods with higher contamination levels, food handling practices, comorbidities, immunodeficiencies, health care access, or other factors.

Characterization of Activation of the Hypothalamic-Pituitary-Adrenal Axis by the Herbicide Atrazine in the Female Rat.

Atrazine (ATR) is a commonly used pre-emergence and early postemergence herbicide. Rats gavaged with ATR and its chlorometabolites desethylatrazine (DEA) and deisopropylatrazine (DIA) respond with a rapid and dose-dependent rise in plasma corticosterone, whereas the major chlorometabolite, diaminochlorotriazine (DACT), has little or no effect on corticosterone levels. In this study, we investigated the possible sites of ATR activation of the hypothalamic-pituitary-adrenal (HPA) axis. ATR treatment had no effect on adrenal weights but altered adrenal morphology. Hypophysectomized rats or rats under dexamethasone suppression did not respond to ATR treatment, suggesting that ATR does not directly stimulate the adrenal gland to induce corticosterone synthesis. Immortalized mouse corticotrophs (AtT-20) and primary rat pituitary cultures were treated with ATR, DEA, DIA, or DACT. None of the compounds induced an increase in ACTH secretion or potentiated ACTH release in conjunction with CRH on ACTH release. In female rats gavaged with ATR, pretreatment with the CRH receptor antagonist astressin completely blocked the ATR-induced rise in corticosterone concentrations, implicating CRH release in ATR-induced HPA activation. Intracerebroventricular infusion of ATR, DEA, and DIA but not DACT at concentrations equivalent to peak plasma concentrations after gavage dosing resulted in an elevation of plasma corticosterone concentrations. However, ATR did not induce c-Fos immunoreactivity in the paraventricular nucleus of the hypothalamus. These results indicate that ATR activates the HPA axis centrally and requires CRH receptor activation, but it does not stimulate cellular pathways associated with CRH neuronal excitation.

Vaccination coverage among foreign-born and U.S.-born adolescents in the United States: Successes and gaps - National Immunization Survey-Teen, 2012-2014.

BACKGROUND: An overall increase has been reported in vaccination rates among adolescents during the past decade. Studies of vaccination coverage have shown disparities when comparing foreign-born and U.S.-born populations among children and adults; however, limited information is available concerning potential disparities in adolescents. METHODS: The National Immunization Survey-Teen is a random-digit-dialed telephone survey of caregivers of adolescents aged 13-17 years, followed by a mail survey to vaccination providers that is used to estimate vaccination coverage among the U.S. population of adolescents. Using the National Immunization Survey-Teen data, we assessed vaccination coverage during 2012-2014 among adolescents for routinely recommended vaccines for this age group (≥1 dose tetanus and diphtheria toxoids and acellular pertussis [Tdap] vaccine, ≥1 dose quadrivalent meningococcal conjugate [MenACWY] vaccine, ≥3 doses human papillomavirus [HPV] vaccine) and for routine childhood vaccination catch-up doses (≥2 doses measles, mumps, and rubella [MMR] vaccine, ≥2 doses varicella vaccine, and ≥3 doses hepatitis B [HepB] vaccine). Vaccination coverage prevalence and vaccination prevalence ratios were estimated. RESULTS: Of the 58,090 respondents included, 3.3% were foreign-born adolescents. Significant differences were observed between foreign-born and U.S.-born adolescents for insurance status, income-to-poverty ratio, education, interview language, and household size. Foreign-born adolescents had significantly lower unadjusted vaccination coverage for HepB (89% vs. 93%), and higher coverage for the recommended ≥3 doses of HPV vaccine among males, compared with U.S.-born adolescents (22% vs. 14%). Adjustment for demographic and socioeconomic factors accounted for the disparity in HPV but not HepB vaccination coverage. CONCLUSIONS: We report comparable unadjusted vaccination coverage among foreign-born and U.S.-born adolescents for Tdap, MenACWY, MMR, ≥2 varicella. Although coverage was high for HepB vaccine, it was significantly lower among foreign-born adolescents, compared with U.S.-born adolescents. HPV and ≥2-dose varicella vaccination coverage were low among both groups.

Demographic and Travel Characteristics of Travel-Associated Zika Virus Infection Case-Patients in San Diego County, California (January 1, 2016-March 31, 2017).

Most Zika disease cases diagnosed in the continental US have been associated with travel to areas with risk of Zika transmission, mainly the Caribbean and Latin America. Limited information has been published about the demographic and travel characteristics of Zika case-patients in the United States, besides their age and gender. During 2016-2017 the County of San Diego Health and Human Services Agency, California, expanded the scope and completeness of demographic and travel information collected from Zika case-patients for public health surveillance purposes. The majority (53.8%) of travel-related Zika virus infection case-patients (n = 78) in the county were Hispanic, significantly higher (p ≤ 0.05) than the 33.0% of Hispanics in the county. Foreign-born residents, mainly from Mexico, were also overrepresented among cases compared to their share in the county population (33.3 vs. 23.0%; p ≤ 0.05). Seventeen (21.8%) patients reported a primary language other than English (14 Spanish). Most case-patients traveled for tourism (54%) or to visit friends and relatives (36%). This surveillance information helps identify higher-risk populations and implement culturally targeted interventions for Zika prevention and control.

Pneumococcal Serotype 5 Colonization Prevalence Among Newly Arrived Unaccompanied Children 1 Year After an Outbreak-Texas, 2015.

In 2014, an acute respiratory illness outbreak affected unaccompanied children from Central America entering the United States; 9% of 774 surveyed children were colonized with Streptococcus pneumoniae serotype 5. In our 2015 follow-up survey of 475 children, serotype 5 was not detected, and an interim recommendation to administer 13-valent pneumococcal conjugate vaccine to all unaccompanied children was discontinued.

Notes from the Field: Outbreak of Zika Virus Disease - American Samoa, 2016.

During December 2015-January 2016, the American Samoa Department of Health (ASDoH) detected through surveillance an increase in the number of cases of acute febrile rash illness. Concurrently, a case of laboratory-confirmed Zika virus infection, a mosquito-borne flavivirus infection documented to cause microcephaly and other severe brain defects in some infants born to women infected during pregnancy (1,2) was reported in a traveler returning to New Zealand from American Samoa. In the absence of local laboratory capacity to test for Zika virus, ASDoH initiated arboviral disease control measures, including public education and vector source reduction campaigns. On February 1, CDC staff members were deployed to American Samoa to assist ASDoH with testing and surveillance efforts.

Psychological interventions for Common Mental Disorders for People Living With HIV in Low- and Middle-Income Countries: systematic review.

OBJECTIVE: To assess the effectiveness of structured psychological interventions against common mental disorders (CMD) in people living with HIV infection (PLWH), in low- and middle-income countries (LMIC). METHODS: Systematic review of psychological interventions for CMD from LMIC for PLWH, with two-stage screening carried out independently by 2 authors. RESULTS: Of 190 studies, 5 met inclusion criteria. These were randomised-controlled trials based on the principles of cognitive behaviour therapy (CBT) and were effective in reducing CMD symptoms in PLWH. Follow-up of study participants ranged from 6 weeks to 12 months with multiple tools utilised to measure the primary outcome. Four studies showed a high risk of bias, while 1 study from Iran met low risk of bias in all 6 domains of the Cochrane risk of bias tool and all 22 items of the CONSORT instrument. CONCLUSION: There is a need for more robust and adequately powered studies to further explore CBT-based interventions in PLWH. Future studies should report on components of the psychological interventions, fidelity measurement and training, including supervision of delivering agents, particularly where lay health workers are the delivering agent.

Comparison of the efficiency and cost of West Nile virus surveillance methods in California.

Surveillance systems for West Nile virus (WNV) combine several methods to determine the location and timing of viral amplification. The value of each surveillance method must be measured against its efficiency and costs to optimize integrated vector management and suppress WNV transmission to the human population. Here we extend previous comparisons of WNV surveillance methods by equitably comparing the most common methods after standardization on the basis of spatial sampling density and costs, and by estimating optimal levels of sampling effort for mosquito traps and sentinel chicken flocks. In general, testing for evidence of viral RNA in mosquitoes and public-reported dead birds resulted in detection of WNV approximately 2-5 weeks earlier than serological monitoring of sentinel chickens at equal spatial sampling density. For a fixed cost, testing of dead birds reported by the public was found to be the most cost effective of the methods, yielding the highest number of positive results per $1000. Increased spatial density of mosquito trapping was associated with more precise estimates of WNV infection prevalence in mosquitoes. Our findings also suggested that the most common chicken flock size of 10 birds could be reduced to six to seven without substantial reductions in timeliness or sensitivity. We conclude that a surveillance system that uses the testing of dead birds reported by the public complemented by strategically timed mosquito and chicken sampling as agency resources allow would detect viral activity efficiently in terms of effort and costs, so long as susceptible bird species that experience a high mortality rate from infection with WNV, such as corvids, are present in the area.

Understanding the structural requirements for activators of the Kef bacterial potassium efflux system.

The potassium efflux system, Kef, protects bacteria against the detrimental effects of electrophilic compounds via acidification of the cytoplasm. Kef is inhibited by glutathione (GSH) but activated by glutathione-S-conjugates (GS-X) formed in the presence of electrophiles. GSH and GS-X bind to overlapping sites on Kef, which are located in a cytosolic regulatory domain. The central paradox of this activation mechanism is that GSH is abundant in cells (at concentrations of ∼10-20 mM), and thus, activating ligands must possess a high differential over GSH in their affinity for Kef. To investigate the structural requirements for binding of a ligand to Kef, a novel fluorescent reporter ligand, S-{[5-(dimethylamino)naphthalen-1-yl]sulfonylaminopropyl} glutathione (DNGSH), was synthesized. By competition assays using DNGSH, complemented by direct binding assays and thermal shift measurements, we show that the well-characterized Kef activator, N-ethylsuccinimido-S-glutathione, has a 10-20-fold higher affinity for Kef than GSH. In contrast, another native ligand that is a poor activator, S-lactoylglutathione, exhibits a similar Kef affinity to GSH. Synthetic ligands were synthesized to contain either rigid or flexible structures and investigated as ligands for Kef. Compounds with rigid structures and high affinity activated Kef. In contrast, flexible ligands with similar binding affinities did not activate Kef. These data provide insight into the structural requirements for Kef gating, paving the way for the development of a screen for potential therapeutic lead compounds targeting the Kef system.

Genes that influence swarming motility and biofilm formation in Variovorax paradoxus EPS.

BACKGROUND: Variovorax paradoxus is an aerobic soil bacterium associated with important biodegradative processes in nature. We use V. paradoxus EPS to study multicellular behaviors on surfaces. METHODOLOGY: We recovered flanking sequence from 123 clones in a Tn5 mutant library, with insertions in 29 different genes, selected based on observed surface behavior phenotypes. We identified three genes, Varpa_4665, Varpa_4680, and Varpa_5900, for further examination. These genes were cloned into pBBR1MCS2 and used to complement the insertion mutants. We also analyzed expression of Varpa_4680 and Varpa_5900 under different growth conditions by qPCR. RESULTS: The 29 genes we identified had diverse predicted functions, many in exopolysaccharide synthesis. Varpa_4680, the most commonly recovered insertion site, encodes a putative N-acetyl-L-fucosamine transferase similar to WbuB. Expression of this gene in trans complemented the mutant fully. Several unique insertions were identified in Varpa_5900, which is one of three predicted pilY1 homologs in the EPS genome. No insertions in the two other putative pilY1 homologs present in the genome were identified. Expression of Varpa_5900 altered the structure of the wild type swarm, as did disruption of the chromosomal gene. The swarming phenotype was complemented by expression of Varpa_5900 from a plasmid, but biofilm formation was not restored. Both Varpa_4680 and Varpa_5900 transcripts were downregulated in biofilms and upregulated during swarming when compared to log phase culture. We identified a putative two component system (Varpa_4664-4665) encoding a response regulator (shkR) and a sensor histidine kinase (shkS), respectively. Biofilm formation increased and swarming was strongly delayed in the Varpa_4665 (shkS) mutant. Complementation of shkS restored the biofilm phenotype but swarming was still delayed. Expression of shkR in trans suppressed biofilm formation in either genetic background, and partially restored swarming in the mutant. CONCLUSIONS: The data presented here point to complex regulation of these surface behaviors.

The regulation of food intake in mammalian hibernators: a review.

One of the most profound hallmarks of mammalian hibernation is the dramatic reduction in food intake during the winter months. Several species of hibernator completely cease food intake (aphagia) for nearly 7 months regardless of ambient temperature and in many cases, whether or not food is available to them. Food intake regulation has been studied in mammals that hibernate for over 50 years and still little is known about the physiological mechanisms that control this important behavior in hibernators. It is well known from lesion experiments in non-hibernators that the hypothalamus is the main brain region controlling food intake and therefore body mass. In hibernators, the regulation of food intake and body mass is presumably governed by a circannual rhythm since there is a clear seasonal rhythm to food intake: animals increase food intake in the summer and early autumn, food intake declines in autumn and actually ceases in winter in many species, and resumes again in spring as food becomes available in the environment. Changes in circulating hormones (e.g., leptin, insulin, and ghrelin), nutrients (glucose, and free fatty acids), and cellular enzymes such as AMP-activated protein kinase (AMPK) have been shown to determine the activity of neurons involved in the food intake pathway. Thus, it appears likely that the food intake pathway is controlled by a variety of inputs, but is also acted upon by upstream regulators that are presumably rhythmic in nature. Current research examining the molecular mechanisms and integration of environmental signals (e.g., temperature and light) with these molecular mechanisms will hopefully shed light on how animals can turn off food intake and survive without eating for months on end.