Topological defects in multi-layered swarming bacteria.

Topological defects, which are singular points in a director field, play a major role in shaping active systems. Here, we experimentally study topological defects and the flow patterns around them, that are formed during the highly rapid dynamics of swarming bacteria. The results are compared to the predictions of two-dimensional active nematics. We show that, even though some of the assumptions underlying the theory do not hold, the swarm dynamics is in agreement with two-dimensional nematic theory. In particular, we look into the multi-layered structure of the swarm, which is an important feature of real, natural colonies, and find a strong coupling between layers. Our results suggest that the defect-charge density is hyperuniform, i.e., that long range density-fluctuations are suppressed.

Evidence Accumulation Rate Moderates the Relationship between Enriched Environment Exposure and Age-Related Response Speed Declines.

Older adults exposed to enriched environments (EEs) maintain relatively higher levels of cognitive function, even in the face of compromised markers of brain health. Response speed (RS) is often used as a simple proxy to measure the preservation of global cognitive function in older adults. However, it is unknown which specific selection, decision, and/or motor processes provide the most specific indices of neurocognitive health. Here, using a simple decision task with electroencephalography (EEG), we found that the efficiency with which an individual accumulates sensory evidence was a critical determinant of the extent to which RS was preserved in older adults (63% female, 37% male). Moreover, the mitigating influence of EE on age-related RS declines was most pronounced when evidence accumulation rates were shallowest. These results suggest that the phenomenon of cognitive reserve, whereby high EE individuals can better tolerate suboptimal brain health to facilitate the preservation of cognitive function, is not just applicable to neuroanatomical indicators of brain aging but can be observed in markers of neurophysiology. Our results suggest that EEG metrics of evidence accumulation may index neurocognitive vulnerability of the aging brain.Significance Statement Response speed in older adults is closely linked with trajectories of cognitive aging. Here, by recording brain activity while individuals perform a simple computer task, we identify a neural metric that is a critical determinant of response speed. Older adults exposed to greater cognitive and social stimulation throughout a lifetime could maintain faster responding, even when this neural metric was impaired. This work suggests EEG is a useful technique for interrogating how a lifetime of stimulation benefits brain health in aging.

Self-Assembly Dynamics of Reconfigurable Colloidal Molecules.

Colloidal molecules are designed to mimic their molecular analogues through their anisotropic shape and interactions. However, current experimental realizations are missing the structural flexibility present in real molecules thereby restricting their use as model systems. We overcome this limitation by assembling reconfigurable colloidal molecules from silica particles functionalized with mobile DNA linkers in high yields. We achieve this by steering the self-assembly pathway toward the formation of finite-sized clusters by employing high number ratios of particles functionalized with complementary DNA strands. The size ratio of the two species of particles provides control over the overall cluster size, i.e., the number of bound particles N, as well as the degree of reconfigurability. The bond flexibility provided by the mobile linkers allows the successful assembly of colloidal clusters with the geometrically expected maximum number of bound particles and shape. We quantitatively examine the self-assembly dynamics of these flexible colloidal molecules by a combination of experiments, agent-based simulations, and an analytical model. Our "flexible colloidal molecules" are exciting building blocks for investigating and exploiting the self-assembly of complex hierarchical structures, photonic crystals, and colloidal metamaterials.

Confinement-induced self-organization in growing bacterial colonies.

We investigate the emergence of global alignment in colonies of dividing rod-shaped cells under confinement. Using molecular dynamics simulations and continuous modeling, we demonstrate that geometrical anisotropies in the confining environment give rise to an imbalance in the normal stresses, which, in turn, drives a collective rearrangement of the cells. This behavior crucially relies on the colony's solid-like mechanical response at short time scales and can be recovered within the framework of active hydrodynamics upon modeling bacterial colonies as growing viscoelastic gels characterized by Maxwell-like stress relaxation.

Cooperative ordering of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA.

During bacterial cell division, the tubulin-homolog FtsZ forms a ring-like structure at the center of the cell. This Z-ring not only organizes the division machinery, but treadmilling of FtsZ filaments was also found to play a key role in distributing proteins at the division site. What regulates the architecture, dynamics and stability of the Z-ring is currently unknown, but FtsZ-associated proteins are known to play an important role. Here, using an in vitro reconstitution approach, we studied how the well-conserved protein ZapA affects FtsZ treadmilling and filament organization into large-scale patterns. Using high-resolution fluorescence microscopy and quantitative image analysis, we found that ZapA cooperatively increases the spatial order of the filament network, but binds only transiently to FtsZ filaments and has no effect on filament length and treadmilling velocity. Together, our data provides a model for how FtsZ-associated proteins can increase the precision and stability of the bacterial cell division machinery in a switch-like manner.

Mono- to Multilayer Transition in Growing Bacterial Colonies.

The transition from monolayers to multilayered structures in bacterial colonies is a fundamental step in biofilm development. Observed across different morphotypes and species, this transition is triggered within freely growing bacterial microcolonies comprising a few hundred cells. Using a combination of numerical simulations and analytical modeling, here we demonstrate that this transition originates from the competition between growth-induced in-plane active stresses and vertical restoring forces, due to the cell-substrate interactions. Using a simple chainlike colony of laterally confined cells, we show that the transition sets when individual cells become unstable to rotations; thus it is localized and mechanically deterministic. Asynchronous cell division renders the process stochastic, so that all the critical parameters that control the onset of the transition are continuously distributed random variables. Here we demonstrate that the occurrence of the first division in the colony can be approximated as a Poisson process in the limit of large cell numbers. This allows us to approximately calculate the probability distribution function of the position and time associated with the first extrusion. The rate of such a Poisson process can be identified as the order parameter of the transition, thus highlighting its mixed deterministic-stochastic nature.

Web App- and Text Message-Based Patient Education in Mohs Micrographic Surgery-A Randomized Controlled Trial.

BACKGROUND: Consent and wound care (WC) videos are used for education in Mohs micrographic surgery (MMS). Postoperative text messaging is poorly studied. OBJECTIVE: Develop and evaluate perioperative resources for MMS patients-video modules (DermPatientEd.com) and postoperative text messaging (DermTexts.com). MATERIALS AND METHODS: A study was conducted on 90 MMS patients. Patients were randomized 1:1:1:1 to videos with text messages, videos-only, text messages-only, or control. Primary outcomes included preoperative anxiety and knowledge of MMS and postoperative care. The secondary outcome included helpfulness/preference of interventions. RESULTS: Patients experienced a 19% reduction in anxiety as measured by a visual analog scale after the MMS video (p = .00062). There was no difference in knowledge after the WC video (p = .21498). Patients were more likely to report the WC video "very helpful" when compared with the pamphlet in understanding postoperative WC (p = .0016). Patients in text messaging groups were not more likely to report the service as "very helpful" when compared with the pamphlet (p = .3566), but preferred to receive WC instructions by text message for future visits (p = .0001). CONCLUSION: These resources proved helpful and effective in reducing preoperative anxiety. Patients prefer text message-based WC instructions over pamphlets after experiencing the service, but do not find them more helpful.

The effect of calorie restriction on mouse skeletal muscle is sex, strain and time-dependent.

Loss of skeletal muscle mass and function occurs with increasing age. Calorie restriction (CR) increases the lifespan of C57Bl/6 mice, but not in the shorter-lived DBA/2 strain. There is some evidence that calorie restriction reduces or delays many of the age-related defects that occur in rodent skeletal muscle. We therefore investigated the effect of short (2.5 month) and longer term (8.5 and 18.5 months) CR on skeletal muscle in male and female C57Bl/6 and DBA/2 mice. We found that short-term CR increased the satellite cell number and collagen VI content of muscle, but resulted in a delayed regenerative response to injury.Consistent with this, the in vitro proliferation of satellite cells derived from these muscles was reduced by CR. The percentage of stromal cells, macrophages, hematopoietic stem cells and fibroadipogenic cells in the mononucleated cell population derived from skeletal muscle was reduced by CR at various stages. But overall, these changes are neither consistent over time, nor between strain and sex. The fact that changes induced by CR do not persist with time and the dissimilarities between the two mouse strains, combined with sex differences, urge caution in applying CR to improve skeletal muscle function across the lifespan in humans.

Patient perceptions of text-messages, email, and video in dermatologic surgery patients.

INTRODUCTION: We developed dermatology patient education videos and a post-operative text message service that could be accessed universally via web based applications. A secondary outcome of the study was to assess patient opinions of text-messages, email, and video in the health care setting which is reported here. METHODS: An investigator-blinded, randomized, controlled intervention was evaluated in 90 nonmelanoma MMS patients at Wake Forest Baptist Dermatology. Patients were randomized 1:1:1:1 for exposure to: 1) videos with text messages, 2) videos only, 3) text messages-only, or 4) standard of care. Assessment measures were obtained by the use of REDCap survey questions during the follow up visit. RESULTS: 1) 67% would like to receive an email with information about the procedure beforehand 2) 98% of patients reported they would like other doctors to use educational videos as a form of patient education 3) 88% of our patients think it is appropriate for physicians to communicate to patients via text message in certain situations. CONCLUSION: Nearly all patients desired physicians to use text-messages and video in their practice and the majority of patients preferred to receive an email with information about their procedure beforehand.

Linear response to leadership, effective temperature, and decision making in flocks.

Large collections of autonomously moving agents, such as animals or micro-organisms, are able to flock coherently in space even in the absence of a central control mechanism. While the direction of the flock resulting from this critical behavior is random, this can be controlled by a small subset of informed individuals acting as leaders of the group. In this article we use the Vicsek model to investigate how flocks respond to leadership and make decisions. Using a combination of numerical simulations and continuous modeling we demonstrate that flocks display a linear response to leadership that can be cast in the framework of the fluctuation-dissipation theorem, identifying an effective temperature reflecting how promptly the flock reacts to the initiative of the leaders. The linear response to leadership also holds in the presence of two groups of informed individuals with competing interests, indicating that the flock's behavioral decision is determined by both the number of leaders and their degree of influence.

Calorie Restriction Attenuates Terminal Differentiation of Immune Cells.

Immune senescence is a natural consequence of aging and may contribute to frailty and loss of homeostasis in later life. Calorie restriction increases healthy life-span in C57BL/6J (but not DBA/2J) mice, but whether this is related to preservation of immune function, and how it interacts with aging, is unclear. We compared phenotypic and functional characteristics of natural killer (NK) cells and T cells, across the lifespan, of calorie-restricted (CR) and control C57BL/6 and DBA/2 mice. Calorie restriction preserves a naïve T cell phenotype and an immature NK cell phenotype as mice age. The splenic T cell populations of CR mice had higher proportions of CD11a-CD44lo cells, lower expression of TRAIL, KLRG1, and CXCR3, and higher expression of CD127, compared to control mice. Similarly, splenic NK cells from CR mice had higher proportions of less differentiated CD11b-CD27+ cells and correspondingly lower proportions of highly differentiated CD11b+CD27-NK cells. Within each of these subsets, cells from CR mice had higher expression of CD127, CD25, TRAIL, NKG2A/C/E, and CXCR3 and lower expression of KLRG1 and Ly49 receptors compared to controls. The effects of calorie restriction on lymphoid cell populations in lung, liver, and lymph nodes were identical to those seen in the spleen, indicating that this is a system-wide effect. The impact of calorie restriction on NK cell and T cell maturation is much more profound than the effect of aging and, indeed, calorie restriction attenuates these age-associated changes. Importantly, the effects of calorie restriction on lymphocyte maturation were more marked in C57BL/6 than in DBA/2J mice indicating that delayed lymphocyte maturation correlates with extended lifespan. These findings have implications for understanding the interaction between nutritional status, immunity, and healthy lifespan in aging populations.

Trends in Mohs surgery from 1995 to 2010: an analysis of nationally representative data.

BACKGROUND: In Mohs surgery, the histologic verification of tumor removal results in a lower rate of cancer recurrence compared with simple excision. Factors associated with the increased use of Mohs surgery are not well characterized. OBJECTIVE: To investigate trends in the utilization of Mohs surgery. METHODS AND MATERIALS: The authors performed a retrospective analysis of the National Ambulatory Medical Care Survey for patient visits associated with Mohs surgery from 1995 to 2010. The authors assessed percentage of skin cancers managed with Mohs surgery, the most common locations of skin cancer managed with Mohs surgery, and patient demographics associated with Mohs surgery. RESULTS: Although there was an upward trend in the use of Mohs surgery (p = .004), a low percentage of skin cancers (average of 10.0%) were managed with this technique. When the surgical location was specified, Mohs surgery was most commonly used for the head and neck region. Demographic groups receiving Mohs surgery at higher rates included African Americans (44.2%) and patients aged 75 to 84 years (12.4%). CONCLUSION: There has been an upward trend in the use of Mohs surgery, particularly in the head and neck region where tissue preservation is essential.

Comparing demographic characteristics and adverse event rates at two dermatologic surgery practices.

BACKGROUND: Patient demographics and operative techniques may contribute to adverse events after surgeries. OBJECTIVE: To identify differences in adverse event rates between different dermatologic surgery centers and potential contributing features affecting these rates. METHODS: Data regarding demographics, procedure type, and adverse events were collected at two dermatologic surgery centers. RESULTS: The most common adverse event at both sites was infection: 2.1% at site 1 versus 0.5% at site 2 (p < .001). Using multivariate logistic regression, procedure type (Mohs surgery), geographic location (being at site 1), older age, and anatomic location of surgery were associated with a higher risk of infection. CONCLUSION: Adverse event rate appears to correlate with patient demographics, procedure type, and setting of surgery more than use of prophylactic antibiotics. Identification of differences in adverse event rates and potential contributing variables at different practices may allow for identification of opportunities to prevent adverse events.

Association of pain and itch with depth of invasion and inflammatory cell constitution in skin cancer: results of a large clinicopathologic study.

IMPORTANCE: This study highlights a simple bedside evaluation of itch and pain for suspicious skin lesions. OBJECTIVE: To examine the correlation of pain and itch with histologic features of skin cancers. DESIGN, SETTING, AND PARTICIPANTS: This large, prospective, clinicopathologic study enrolled patients who filled out questionnaires that assessed itch and pain intensity of their skin tumors at the time of excision. Study participants were from the patient population presenting to the Department of Dermatology surgical unit at Wake Forest University Baptist Medical Center from July 1, 2010, through March 31, 2011. Study participants included 268 patients, representing 339 histopathologically confirmed cutaneous neoplasms. The following skin cancer subtypes were represented in this analysis: 166 basal cell carcinomas, 146 squamous cell carcinomas, and 27 melanomas. MAIN OUTCOMES AND MEASURES: Itch and pain associated with skin cancer at the time of excision ranked on an 11-point (score range, 0-10) numerical visual analog scale and histopathologic analysis for each neoplasm (assessment of the amount and type of inflammation, ulceration, perineural invasion, and depth of invasion). RESULTS: The prevalence of itch and pain across all skin cancers was 36.9% and 28.2%, respectively. However, these symptoms were mostly absent in melanomas. Pain intensity was significantly associated with the degree of inflammation (mild or none vs moderate or marked; P < .001), presence of neutrophils in the inflammatory infiltrate (predominantly mononuclear vs mixed or neutrophilic; P = .003), presence of eosinophils (present vs absent; P = .007), ulceration (yes vs no; P = .003), perineural invasion (yes vs no; P < .001), depth of invasion (P = .001), and largest diameter length of skin lesion (P < .003). Itch intensity was significantly associated with the degree of inflammation (mild or none vs moderate or marked; P = .001) and the presence of eosinophils (present vs absent; P = .02). CONCLUSIONS AND RELEVANCE: These findings support the theory that itch emanates from the upper layers of the skin, whereas pain is associated with deeper processes. This study also reports that a simple bedside assessment for the presence and intensity of pain or itch is an easily implementable tool for physicians evaluating suspicious skin lesions.

Role of projection in the control of bird flocks.

Swarming is a conspicuous behavioral trait observed in bird flocks, fish shoals, insect swarms, and mammal herds. It is thought to improve collective awareness and offer protection from predators. Many current models involve the hypothesis that information coordinating motion is exchanged among neighbors. We argue that such local interactions alone are insufficient to explain the organization of large flocks of birds and that the mechanism for the exchange of long-range information necessary to control their density remains unknown. We show that large flocks self-organize to the maximum density at which a typical individual still can see out of the flock in many directions. Such flocks are marginally opaque--an external observer also still can see a substantial fraction of sky through the flock. Although this seems intuitive, we show it need not be the case; flocks might easily be highly diffuse or entirely opaque. The emergence of marginal opacity strongly constrains how individuals interact with one another within large swarms. It also provides a mechanism for global interactions: an individual can respond to the projection of the flock that it sees. This provides for faster information transfer and hence rapid flock dynamics, another advantage over local models. From a behavioral perspective, it optimizes the information available to each bird while maintaining the protection of a dense, coherent flock.

DNA methylation analysis of murine hematopoietic side population cells during aging.

Stem cells have been found in most tissues/organs. These somatic stem cells produce replacements for lost and damaged cells, and it is not completely understood how this regenerative capacity becomes diminished during aging. To study the possible involvement of epigenetic changes in somatic stem cell aging, we used murine hematopoiesis as a model system. Hematopoietic stem cells (HSCs) were enriched for via Hoechst exclusion activity (SP-HSC) from young, medium-aged and old mice and subjected to comprehensive, global methylome (MeDIP-seq) analysis. With age, we observed a global loss of DNA methylation of approximately 5%, but an increase in methylation at some CpG islands. Just over 100 significant (FDR<0.2) aging-specific differentially methylated regions (aDMRs) were identified, which are surprisingly few considering the profound age-based changes that occur in HSC biology. Interestingly, the polycomb repressive complex -2 (PCRC2) target genes Kiss1r, Nav2 and Hsf4 were hypermethylated with age. The promoter for the Sdpr gene was determined to be progressively hypomethylated with age. This occurred concurrently with an increase in gene expression with age. To explore this relationship further, we cultured isolated SP-HSC in the presence of 5-aza-deoxycytdine and demonstrated a negative correlation between Sdpr promoter methylation and gene expression. We report that DNA methylation patterns are well preserved during hematopoietic stem cell aging, confirm that PCRC2 targets are increasingly methylated with age, and suggest that SDPR expression changes with age in HSCs may be regulated via age-based alterations in DNA methylation.

Quantifying and characterizing adverse events in dermatologic surgery.

BACKGROUND: Although office-based dermatologic procedures are generally considered safe, there is a lack of prospective data on the rate of adverse events (AEs) associated with these procedures. OBJECTIVE: To determine the frequency of AEs after dermatologic surgery and to characterize the most commonly encountered AEs. METHODS: A web-based interface was designed to track AEs with the input of four dermatologic surgeons. Patient demographic and operative data were collected at the time of the dermatologic surgery procedure. AEs occurring at any time during the data collection period were logged according to an a priori categorization scheme. RESULTS: The AE rate was 2.0% in this series of 2,418 subjects undergoing dermatologic surgery from February 1 through December 14, 2010. The most commonly reported AEs were suspicion of infection (64%), postoperative hemorrhage (20%), and wound dehiscence (8%). Suspicion of infection was slightly less frequent in subjects who received prophylactic preoperative antibiotics (0.4%) than in those who did not (1.5%, p = .07). There were no serious AEs and no deaths. CONCLUSION: AEs are uncommon after office-based dermatologic surgery procedures. Preoperative antibiotics may further decrease the infection rate after dermatologic surgery, but the risks and benefits must be weighed given the already low AE rate.

Incidence, risk factors, and preventative management of skin cancers in organ transplant recipients: a review of single- and multicenter retrospective studies from 2006 to 2010.

BACKGROUND: Organ transplant recipients (OTRs) taking immunosuppressants are at high risk of skin cancer, which is the most common malignant condition in OTRs, so dermatologic surveillance is important for OTRs. OBJECTIVES: To characterize the most common skin cancers arising from chronic immunosuppression in OTRs. METHODS: A PubMed search for retrospective single- and multicenter studies reporting skin cancer incidence from 2006 to 2010 was undertaken. Data regarding each study's immunosuppressive regimen, affected skin cancer cohort, and associated risk factors were extracted. RESULTS: Thirty-six articles that met our inclusion criteria reported incidences of nonmelanoma skin cancer (NMSC), Kaposi's sarcoma, melanoma, and Merkel cell carcinoma. NMSC was the most commonly reported cancer of all skin cancers after transplantation. Common risk factors were sex, age, sunlight exposure, and immunosuppressive agent-related (duration, type). CONCLUSION: Sun education programs and frequent screenings in organ transplant clinics have provided the best preventative strategies after transplantation, although the characteristics of the immunosuppressive regimen also play an important role. Thus, the adjuvant strategy of modifying immunosuppression may be effective when confronting severe transplant-associated skin cancer. Although the decision-making process for curbing levels of immunosuppression is difficult, further long-term, randomized controlled studies should assess the effect of using less immunosuppressant medication while preserving graft function.