'Anxious fluctuators' a subgroup of Parkinson's disease with high anxiety and problematic on-off fluctuations.

Anxiety that occurs in association with on-off dopamine medication fluctuations is a major cause of distress, dysfunction, and lower quality of life in people with Parkinson's disease (PD). However, the association between anxiety and on-off fluctuations is poorly understood and it is difficult to predict which patients will suffer from this atypical form of anxiety. To understand whether fluctuating anxiety in PD exists as part of an endophenotype that is associated with other signs or symptoms, we prospectively assessed the change in anxiety and a battery of clinical variables when transitioning from the off-dopamine medication state to the on state in 200 people with PD. We performed latent profile analysis with observed variables as latent profile indicators measuring the on-off-state difference in anxiety, depression, motor function, daily functioning, and the wearing off questionnaire 19 item scale (WOQ-19) in order to model unobserved (i.e., latent) profiles. A two-class model produced the best fit. The majority of participants, 69%, were categorized as having a 'typical on-off response' compared to a second profile constituting 31% of the sample who experienced a worsening in anxiety in the off state that was three times that of other participants. This profile referred to as "anxious fluctuators" had a Hamilton Anxiety Rating Scale change between the off and on medication state of 10.22(32.85) compared to 3.27 (7.62), higher depression scores, greater disability and was less likely to improve on select WOQ-19 items when in the on-state. Anxious fluctuators were more likely to be male and have a family history of anxiety disorder. Given the adverse impact of this profile we believe it may be important to distinguish patients with a typical on-off response from those with this more problematic course of fluctuations.

"Pseudo-syndromes" associated with Parkinson disease, dementia, apathy, anxiety, and depression.

PURPOSE OF REVIEW: Physicians treating patients with Parkinson disease must evaluate not only motor symptoms but also acquire expertise in assessing the complex behavioral features that often accompany the disease, such as dementia, apathy, anxiety, and depression. RECENT FINDINGS: There is a risk of diagnostic confusion and error because many of the behavioral and motor symptoms accentuate, overlap, or mimic each other. SUMMARY: Awareness of potential diagnostic pitfalls and "pseudo-syndromes" should lead to more accurate clinical assessment and better care for our patients.

The Airplane Cabin Microbiome.

Serving over three billion passengers annually, air travel serves as a conduit for infectious disease spread, including emerging infections and pandemics. Over two dozen cases of in-flight transmissions have been documented. To understand these risks, a characterization of the airplane cabin microbiome is necessary. Our study team collected 229 environmental samples on ten transcontinental US flights with subsequent 16S rRNA sequencing. We found that bacterial communities were largely derived from human skin and oral commensals, as well as environmental generalist bacteria. We identified clear signatures for air versus touch surface microbiome, but not for individual types of touch surfaces. We also found large flight-to-flight beta diversity variations with no distinguishing signatures of individual flights, rather a high between-flight diversity for all touch surfaces and particularly for air samples. There was no systematic pattern of microbial community change from pre- to post-flight. Our findings are similar to those of other recent studies of the microbiome of built environments. In summary, the airplane cabin microbiome has immense airplane to airplane variability. The vast majority of airplane-associated microbes are human commensals or non-pathogenic, and the results provide a baseline for non-crisis-level airplane microbiome conditions.

Leaky resistance and the conditions for the existence of lytic bacteriophage.

In experimental cultures, when bacteria are mixed with lytic (virulent) bacteriophage, bacterial cells resistant to the phage commonly emerge and become the dominant population of bacteria. Following the ascent of resistant mutants, the densities of bacteria in these simple communities become limited by resources rather than the phage. Despite the evolution of resistant hosts, upon which the phage cannot replicate, the lytic phage population is most commonly maintained in an apparently stable state with the resistant bacteria. Several mechanisms have been put forward to account for this result. Here we report the results of population dynamic/evolution experiments with a virulent mutant of phage Lambda, λVIR, and Escherichia coli in serial transfer cultures. We show that, following the ascent of λVIR-resistant bacteria, λVIR is maintained in the majority of cases in maltose-limited minimal media and in all cases in nutrient-rich broth. Using mathematical models and experiments, we show that the dominant mechanism responsible for maintenance of λVIR in these resource-limited populations dominated by resistant E. coli is a high rate of either phenotypic or genetic transition from resistance to susceptibility-a hitherto undemonstrated mechanism we term "leaky resistance." We discuss the implications of leaky resistance to our understanding of the conditions for the maintenance of phage in populations of bacteria-their "existence conditions."

Pharmacodynamic considerations of collateral sensitivity in design of antibiotic treatment regimen.

INTRODUCTION: Antibiotics have greatly reduced the morbidity and mortality due to infectious diseases. Although antibiotic resistance is not a new problem, its breadth now constitutes a significant threat to human health. One strategy to help combat resistance is to find novel ways to use existing drugs, even those that display high rates of resistance. For the pathogens Escherichia coli and Pseudomonas aeruginosa, pairs of antibiotics have been identified for which evolution of resistance to drug A increases sensitivity to drug B and vice versa. These research groups have proposed cycling such pairs to treat infections, and similar treatment strategies are being investigated for various cancer forms as well. While an exciting treatment prospect, no cycling experiments have yet been performed with consideration of pharmacokinetics and pharmacodynamics. To test the plausibility of such schemes and optimize them, we create a mathematical model with explicit pharmacokinetic/pharmacodynamic considerations. MATERIALS AND METHODS: We evaluate antibiotic cycling protocols using pairs of such antibiotics and investigate the speed of ascent of multiply resistant mutants. RESULTS: Our analyses show that when using low concentrations of antibiotics, treatment failure will always occur due to the rapid ascent and fixation of resistant mutants. However, moderate to high concentrations of some combinations of bacteriostatic and bactericidal antibiotics with multiday cycling prevent resistance from developing and increase the likelihood of treatment success. CONCLUSION: Our results call for guarded optimism in application and development of such treatment protocols.

Behaviors, movements, and transmission of droplet-mediated respiratory diseases during transcontinental airline flights.

With over 3 billion airline passengers annually, the inflight transmission of infectious diseases is an important global health concern. Over a dozen cases of inflight transmission of serious infections have been documented, and air travel can serve as a conduit for the rapid spread of newly emerging infections and pandemics. Despite sensational media stories and anecdotes, the risks of transmission of respiratory viruses in an airplane cabin are unknown. Movements of passengers and crew may facilitate disease transmission. On 10 transcontinental US flights, we chronicled behaviors and movements of individuals in the economy cabin on single-aisle aircraft. We simulated transmission during flight based on these data. Our results indicate there is low probability of direct transmission to passengers not seated in close proximity to an infectious passenger. This data-driven, dynamic network transmission model of droplet-mediated respiratory disease is unique. To measure the true pathogen burden, our team collected 229 environmental samples during the flights. Although eight flights were during Influenza season, all qPCR assays for 18 common respiratory viruses were negative.

A Numbers Game: Ribosome Densities, Bacterial Growth, and Antibiotic-Mediated Stasis and Death.

We postulate that the inhibition of growth and low rates of mortality of bacteria exposed to ribosome-binding antibiotics deemed bacteriostatic can be attributed almost uniquely to these drugs reducing the number of ribosomes contributing to protein synthesis, i.e., the number of effective ribosomes. We tested this hypothesis with Escherichia coli K-12 MG1655 and constructs that had been deleted for 1 to 6 of the 7 rRNA (rrn) operons. In the absence of antibiotics, constructs with fewer rrn operons have lower maximum growth rates and longer lag phases than those with more ribosomal operons. In the presence of the ribosome-binding "bacteriostatic" antibiotics tetracycline, chloramphenicol, and azithromycin, E. coli strains with 1 and 2 rrn operons are killed at a substantially higher rate than those with more rrn operons. This increase in the susceptibility of E. coli with fewer rrn operons to killing by ribosome-targeting bacteriostatic antibiotics is not reflected in their greater sensitivity to killing by the bactericidal antibiotic ciprofloxacin, which does not target ribosomes, but also to killing by gentamicin, which does. Finally, when such strains are exposed to these ribosome-targeting bacteriostatic antibiotics, the time before these bacteria start to grow again when the drugs are removed, referred to as the post-antibiotic effect (PAE), is markedly greater for constructs with fewer rrn operons than for those with more rrn operons. We interpret the results of these other experiments reported here as support for the hypothesis that the reduction in the effective number of ribosomes due to binding to these structures provides a sufficient explanation for the action of bacteriostatic antibiotics that target these structures. IMPORTANCE: Chemotherapeutic agents, including antibiotics, have been used for more than a century; nevertheless, there are still major gaps in our understanding of how these drugs operate which limit future advances in antibacterial chemotherapy. Although the molecular mechanisms by which antibiotics bind to their target structures are largely known, fundamental questions about how these drugs actually kill and/or inhibit the replication of bacteria remain unanswered and subjects of controversy. We postulate that for the broad class of ribosome-binding bacteriostatic antibiotics, their reducing the number of active (functional) ribosomes per cell provides a sufficient explanation for the abatement of replication and the low rate of decline in densities of viable cells of bacteria exposed to these drugs. Using E. coli K-12 constructs with deletions of from one to six of the seven ribosome-RNA operons and the ribosome-binding bacteriostatic antibiotics tetracycline, chloramphenicol, and azithromycin, we tested this hypothesis. The results of our experiments are consistent with this "numbers game" hypothesis.

Controlling viral outbreaks: Quantitative strategies.

Preparing for and responding to outbreaks of serious livestock infectious diseases are critical measures to safeguard animal health, public health, and food supply. Almost all of the current control strategies are empirical, and mass culling or "stamping out" is frequently the principal strategy for controlling epidemics. However, there are ethical, ecological, and economic reasons to consider less drastic control strategies. Here we use modeling to quantitatively study the efficacy of different control measures for viral outbreaks, where the infectiousness, transmissibility and death rate of animals commonly depends on their viral load. We develop a broad theoretical framework for exploring and understanding this heterogeneity. The model includes both direct transmission from infectious animals and indirect transmission from an environmental reservoir. We then incorporate a large variety of control measures, including vaccination, antivirals, isolation, environmental disinfection, and several forms of culling, which may result in fewer culled animals. We provide explicit formulae for the basic reproduction number, R0, for each intervention and for combinations. We evaluate the control methods for a realistic simulated outbreak of low pathogenic avian influenza on a mid-sized turkey farm. In this simulated outbreak, culling results in more total dead birds and dramatically more when culling all of the infected birds.

Job attitudes, job satisfaction, and job affect: A century of continuity and of change.

Over the past 100 years, research on job attitudes has improved in the sophistication of methods and in the productive use of theory as a basis for fundamental research into questions of work psychology. Early research incorporated a diversity of methods for measuring potential predictors and outcomes of job attitudes. Over time, methods for statistically assessing these relationships became more rigorous, but the field also became narrower. In recent years, developments in theory and methodology have reinvigorated research, which now addresses a rich panoply of topics related to the daily flow of affect, the complexity of personal motives and dispositions, and the complex interplay of attitude objects and motivation in shaping behavior. Despite these apparent changes, a review of the concepts and substantive arguments that underpin this literature have remained remarkably consistent. We conclude by discussing how we expect that these major themes will be addressed in the future, emphasizing topics that have proven to be enduring guides for understanding the ways that people construe and react to their appraisals of their work. (PsycINFO Database Record

Personality and reported quality of life in Parkinson's disease.

OBJECTIVE: Personality affects an individual's ability to cope with the burden of chronic disease. However, the impact of personality on quality of life (QoL) in Parkinson's disease (PD) is not well characterized. The goal of this study is to determine the effect of personality on QoL in PD. METHODS: The study included 92 patients with idiopathic PD from Baltimore-Washington area movement disorder neurology clinics. QoL was assessed using the 37-item Parkinson's disease Quality of Life Questionnaire (PDQL) total score, and the Neuroticism-Extraversion-Openness Inventory was used to determine personality traits. RESULTS: Step-wise regression models examined the contribution of personality, depression, demographic, and PD variables on PDQL-assessed QoL. Neuroticism, conscientiousness, years of education, and depression explained 42% of the variance in the PDQL total score after adjusting for other disease variables. High neuroticism (ß = -0.727, 95% confidence interval (CI) -1.125, -0.328, p < 0.0001) and depression (ß = -9.058, 95%CI -17.46, -0.657, p = 0.035) negatively affected the PDQL, while high conscientiousness (ß = 0.468, 95%CI 0.078, 0.858, p = 0.019), and years of education (ß = 1.441, 95%CI 0.371, 2.510, p = 0.009) were positive factors. CONCLUSIONS: Personality can have a positive or negative influence on QoL in PD. PD patients with otherwise similar disease burdens and depressive symptoms may experience different levels of QoL depending on the level of neurotic or conscientious personality traits. Therefore, when interpreting patient responses on the PDQL, it is important to understand whether they reflect aspects of PD, that is, motor impairment and depression, which are amenable to treatment or whether they reflect personality traits.

Clinical Pearls in Tremor and Other Hyperkinetic Movement Disorders.

Hyperkinetic movements, such as tremor, myoclonus, chorea, and dystonia, occur in many neurologic and medical conditions. Accurate clinical evaluation is the important first step for the proper diagnosis and treatment of patients with abnormal movements.

On the 2-Row Rule for Infectious Disease Transmission on Aircraft.

BACKGROUND: With over two billion airline passengers annually, in-flight transmission of infectious diseases is an important global health concern. Many instances of in-flight transmission have been documented, but the relative influence of the many factors (see below) affecting in-flight transmission has not been quantified. Long-standing guidance by public health agencies is that the primary transmission risk associated with air travel for most respiratory infectious diseases is associated with sitting within two rows of an infectious passenger. The effect of proximity may be one of these factors. OBJECTIVE: The aim of this study was to determine the risk of infection within and beyond the 2-row rule given by public health guidance. METHODS: We searched the literature for reports of in-flight transmission of infection which included seat maps indicating where the infectious and infected passengers were seated. FINDINGS: There is a ∼ 6% risk to passengers seated within the 2-rows of infected individual(s) and there is ∼ 2% risk to passengers seated beyond 2-rows from the infectious individual. DISCUSSION: Contact tracing limited to passengers within 2-rows of the infectious individual(s) could fail to detect other cases of infections. This has important consequences for assessing the spread of infectious diseases. CONCLUSIONS: Infection at a distance from the index case indicates other factors, such as airflow, movement of passenger/crew members, fomites and contacts between passengers in the departure gate before boarding, or after deplaning, are involved.

Malthusian Parameters as Estimators of the Fitness of Microbes: A Cautionary Tale about the Low Side of High Throughput.

The maximum exponential growth rate, the Malthusian parameter (MP), is commonly used as a measure of fitness in experimental studies of adaptive evolution and of the effects of antibiotic resistance and other genes on the fitness of planktonic microbes. Thanks to automated, multi-well optical density plate readers and computers, with little hands-on effort investigators can readily obtain hundreds of estimates of MPs in less than a day. Here we compare estimates of the relative fitness of antibiotic susceptible and resistant strains of E. coli, Pseudomonas aeruginosa and Staphylococcus aureus based on MP data obtained with automated multi-well plate readers with the results from pairwise competition experiments. This leads us to question the reliability of estimates of MP obtained with these high throughput devices and the utility of these estimates of the maximum growth rates to detect fitness differences.

Application of depression rating scales in patients with Parkinson's disease with and without co-Occurring anxiety.

BACKGROUND: In patients with Parkinson's disease (PD), depressive symptom rating scales facilitate identification of depressive disorders, which are common and disabling. Anxiety disturbances in PD, which lack valid assessment scales, frequently co-occur with PD-depression, are under-recognized, and require different interventions than depressive disorders. Whether high anxiety rates in PD confound depression scale performance or if any depression scales also predict anxiety disturbances is not known. OBJECTIVE: To test the impact of co-occurring anxiety disorders on psychometric properties of depression rating scales in depressed PD patients and compare disability between PD patients with anxiety, depression, and comorbid anxiety and depressive disorders. METHODS: PD subjects (n = 229) completed self-report and clinician-administered depression scales. Receiver operating characteristic curves were developed to estimate psychometric properties of each scale in those with depression alone, anxiety alone, and comorbid depression and anxiety. Between-group differences on all measures were examined. RESULTS: Comorbid anxiety did not affect the psychometric properties of any scale when identifying depressive disorders, but is associated with greater symptom severity and disability. Depression-scale scores were not significantly different between subjects with anxiety disorders only and those without depressive or anxiety diagnoses. CONCLUSIONS: Co-occurring anxiety disorders do not impact performance of depression rating scales in depressed PD patients. However, depression rating scales do not adequately identify anxiety disturbances alone or in patients with depression.

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.

Get the news out loudly and quickly: the influence of the media on limiting emerging infectious disease outbreaks.

During outbreaks of infectious diseases with high morbidity and mortality, individuals closely follow media reports of the outbreak. Many will attempt to minimize contacts with other individuals in order to protect themselves from infection and possibly death. This process is called social distancing. Social distancing strategies include restricting socializing and travel, and using barrier protections. We use modeling to show that for short-term outbreaks, social distancing can have a large influence on reducing outbreak morbidity and mortality. In particular, public health agencies working together with the media can significantly reduce the severity of an outbreak by providing timely accounts of new infections and deaths. Our models show that the most effective strategy to reduce infections is to provide this information as early as possible, though providing it well into the course of the outbreak can still have a significant effect. However, our models for long-term outbreaks indicate that reporting historic infection data can result in more infections than with no reporting at all. We examine three types of media influence and we illustrate the media influence with a simulated outbreak of a generic emerging infectious disease in a small city. Social distancing can never be complete; however, for a spectrum of outbreaks, we show that leaving isolation (stopping applying social distancing measures) for up to 4 hours each day has modest effect on the overall morbidity and mortality.

A perspective on multiple waves of influenza pandemics.

BACKGROUND: A striking characteristic of the past four influenza pandemic outbreaks in the United States has been the multiple waves of infections. However, the mechanisms responsible for the multiple waves of influenza or other acute infectious diseases are uncertain. Understanding these mechanisms could provide knowledge for health authorities to develop and implement prevention and control strategies. MATERIALS AND METHODS: We exhibit five distinct mechanisms, each of which can generate two waves of infections for an acute infectious disease. The first two mechanisms capture changes in virus transmissibility and behavioral changes. The third mechanism involves population heterogeneity (e.g., demography, geography), where each wave spreads through one sub-population. The fourth mechanism is virus mutation which causes delayed susceptibility of individuals. The fifth mechanism is waning immunity. Each mechanism is incorporated into separate mathematical models, and outbreaks are then simulated. We use the models to examine the effects of the initial number of infected individuals (e.g., border control at the beginning of the outbreak) and the timing of and amount of available vaccinations. RESULTS: Four models, individually or in any combination, reproduce the two waves of the 2009 H1N1 pandemic in the United States, both qualitatively and quantitatively. One model reproduces the two waves only qualitatively. All models indicate that significantly reducing or delaying the initial numbers of infected individuals would have little impact on the attack rate. Instead, this reduction or delay results in a single wave as opposed to two waves. Furthermore, four of these models also indicate that a vaccination program started earlier than October 2009 (when the H1N1 vaccine was initially distributed) could have eliminated the second wave of infection, while more vaccine available starting in October would not have eliminated the second wave.

Affect spin and the emotion regulation process at work.

Regulating emotions is one of the most depleting activities that customer service employees are asked to do, but not all employees get burned out by the end of an emotionally laborious day. In the current study, affect spin-the trait variability of an individual's affective states-was hypothesized to increase strain and fatigue associated with emotion regulation, yet weaken the relation between recent strain and immediate fatigue. The authors examined these hypotheses in an experience sampling study of restaurant servers. Sixty-three servers completed surveys on 4 occasions during each of approximately 10 shifts (2,051 total surveys). Multilevel analyses supported the underlying model linking emotion regulation to fatigue at work as well as the hypothesized role of affect spin. Although affect spin reflects greater reactivity to affective events, it also provides some degree of a buffer from the fatiguing effects of these events.