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.

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.

Evaluation of an Inverse Method for Quantifying Spatially Variable Mechanics.

Soft biological tissues often function as highly deformable membranes in vivo and exhibit impressive mechanical behavior effectively characterized by planar biaxial testing. The Generalized Anisotropic Inverse Mechanics (GAIM) method links full-field deformations and boundary forces from mechanical testing to quantify material properties of soft, anisotropic, heterogeneous tissues. In this study, we introduced an orthotropic constraint to GAIM to improve the quality and physical significance of its mechanical characterizations. We evaluated the updated GAIM method using simulated and experimental biaxial testing datasets obtained from soft tissue analogs (PDMS and TissueMend) with well-defined mechanical properties. GAIM produced stiffnesses (first Kelvin moduli, K1) that agreed well with previously published Young's moduli of PDMS samples. It also matched the stiffness moduli determined via uniaxial testing for TissueMend, a collagen-rich patch intended for tendon repair. We then conducted the first biaxial testing of TissueMend and confirmed that the sample was mechanically anisotropic via a relative anisotropy metric produced by GAIM. Next, we demonstrated the benefits of full-field laser micrometry in distinguishing between spatial variations in thickness and stiffness. Finally, we conducted an analysis to verify that results were independent of partitioning scheme. The success of the newly implemented constraints on GAIM suggests notable potential for applying this tool to soft tissues, particularly following the onset of pathologies that induce mechanical and structural heterogeneities.

Interest, Concerns, and Attitudes Among Men Who Have Sex With Men and Health Care Providers Toward Prophylactic Use of Doxycycline Against Chlamydia trachomatis Infections and Syphilis.

BACKGROUND: Prophylactic administration of doxycycline is regarded as a potential new public health strategy to combat the rising rates of Chlamydia trachomatis infections and syphilis among men who have sex with men. We conducted a survey-based study to evaluate how community members and health care providers in Southern California would perceive doxycycline preexposure/postexposure prophylaxis (PrEP/PEP) to predict its acceptability and identify potential areas of concern. METHODS: We conducted an online cross-sectional survey among community members who identify as men who have sex with men and health care providers with prescribing authority in Southern California to investigate the current attitudes toward doxycycline PrEP/PEP, including their willingness to accept. We analyzed the data using descriptive statistics and binary logistic regression. RESULTS: Among 212 enrolled community member participants, 67.5% indicated they would take doxycycline PrEP/PEP if offered by their provider. Higher acceptability was significantly associated with several characteristics, including recent history of bacterial sexually transmitted infection diagnosis and current use of HIV PrEP. For health care providers, 89.5% of 76 enrolled participants expressed willingness to prescribe doxycycline PrEP/PEP to their patients if recommended by the Centers for Disease Control and Prevention, but only 43.4% were willing if not. Both community members and health care providers demonstrated high levels of concern toward possible drug resistance. CONCLUSIONS: Doxycycline PrEP/PEP as a preventive strategy against chlamydial infections and syphilis would likely be accepted among community members and health care providers. Clear guidelines from public health officials and further clarification on the strategy's potential impact on developing drug resistance may be necessary to ensure successful implementation.

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.

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.

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.

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.

Electrosurgery: part I. Basics and principles.

The term electrosurgery (also called radiofrequency surgery) refers to the passage of high-frequency alternating electrical current through the tissue in order to achieve a specific surgical effect. Although the mechanism behind electrosurgery is not completely understood, heat production and thermal tissue damage is responsible for at least the majority--if not all--of the tissue effects in electrosurgery. Adjacent to the active electrode, tissue resistance to the passage of current converts electrical energy to heat. The only variable that determines the final tissue effects of a current is the depth and the rate at which heat is produced. Electrocoagulation occurs when tissue is heated below the boiling point and undergoes thermal denaturation. An additional slow increase in temperature leads to vaporization of the water content in the coagulated tissue and tissue drying, a process called desiccation. A sudden increase in tissue temperature above the boiling point causes rapid explosive vaporization of the water content in the tissue adjacent to the electrode, which leads to tissue fragmentation and cutting.

Electrosurgery: part II. Technology, applications, and safety of electrosurgical devices.

Electrosurgical currents can be delivered to tissue in monopolar or bipolar and monoterminal or biterminal modes, with the primary difference between these modes being their safety profiles. A monopolar electrosurgical circuit includes an active electrode and a dispersive (return) electrode, while there are 2 active electrodes in bipolar mode. In monoterminal mode, there is an active electrode, but there is no dispersive electrode connected to the patient's body and instead the earth acts as the return electrode. Biterminal mode uses a dispersive electrode connected to the patient's body, has a higher maximum power, and can be safer than monoterminal mode in certain situations. Electrosurgical units have different technologies for controlling the output power and for providing safety. A thorough understanding of these technologies helps with a better selection of the appropriate surgical generator and modes.

Characterization of Decellularized Plant Leaf as an Emerging Biomaterial Platform.

Decellularized plants have emerged as promising biomaterials for cell culture and tissue engineering applications due to their distinct material characteristics. This study explores the biochemical, mechanical, and structural properties of decellularized leaves that make them useful as biomaterials for cell culture. Five monocot leaf species were decellularized via alkali treatment, resulting in the effective removal of DNA and proteins. The Van Soest method was used to quantitatively evaluate the changes in cellulose, hemicellulose, and lignin content during decellularization. Tensile tests revealed considerable variations in mechanical strength depending on the plant species, the decellularization state, and the direction of applied mechanical force. Decellularized monocot leaves exhibited a notable reduction in mechanical strength and anisotropic properties depending on the leaf orientation. Imaging revealed inherent microgrooves on the epidermis of the monocot leaves. Permeability studies, including water uptake and biomolecule transport through decellularized leaves, confirmed excellent water uptake capability but limited biomolecule transport. Lastly, the plants were enzymatically degradable using typical plant enzymes, which were minimally cytotoxic to mammalian cells. Taken together, the features of decellularized plant leaves characterized in this study suggest ways in which they can be useful in cell culture and tissue engineering applications.

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.

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.

Don't go breakin' my heart: cardioprotective alterations to the mechanical and structural properties of reperfused myocardium during post-infarction inflammation.

Myocardial infarctions (MIs) kickstart an intense inflammatory response resulting in extracellular matrix (ECM) degradation, wall thinning, and chamber dilation that leaves the heart susceptible to rupture. Reperfusion therapy is one of the most effective strategies for limiting adverse effects of MIs, but is a challenge to administer in a timely manner. Late reperfusion therapy (LRT; 3 + hours post-MI) does not limit infarct size, but does reduce incidences of post-MI rupture and improves long-term patient outcomes. Foundational studies employing LRT in the mid-twentieth century revealed beneficial reductions in infarct expansion, aneurysm formation, and left ventricle dysfunction. The mechanism by which LRT acts, however, is undefined. Structural analyses, relying largely on one-dimensional estimates of ECM composition, have found few differences in collagen content between LRT and permanently occluded animal models when using homogeneous samples from infarct cores. Uniaxial testing, on the other hand, revealed slight reductions in stiffness early in inflammation, followed soon after by an enhanced resistance to failure for cases of LRT. The use of one-dimensional estimates of ECM organization and gross mechanical function have resulted in a poor understanding of the infarct's spatially variable mechanical and structural anisotropy. To resolve these gaps in literature, future work employing full-field mechanical, structural, and cellular analyses is needed to better define the spatiotemporal post-MI alterations occurring during the inflammatory phase of healing and how they are impacted following reperfusion therapy. In turn, these studies may reveal how LRT affects the likelihood of rupture and inspire novel approaches to guide scar formation.

Combining Unique Planar Biaxial Testing with Full-Field Thickness and Displacement Measurement for Spatial Characterization of Soft Tissues.

Soft tissues rely on the incredible complexity of their microstructure for proper function. Local variations in material properties arise as tissues develop and adapt, often in response to changes in loading. A barrier to investigating the heterogeneous nature of soft tissues is the difficulty of developing experimental protocols and analysis tools that can accurately capture spatial variations in mechanical behavior. In this article, we detail protocols enabling mechanical characterizations of anisotropic, heterogeneous soft tissues or tissue analogs. We present a series of mechanical tests designed to maximize inhomogeneous strain fields and in-plane shear forces. A customized, 3D-printable gripping system reduces tissue handling and enhances shear. High-resolution imaging and laser micrometry capture full-field displacement and thickness, respectively. As the equipment necessary to conduct these protocols is commercially available, the experimental methods presented offer an accessible route toward addressing heterogeneity. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Unique biaxial testing of soft tissues and tissue analogs Basic Protocol 2: Full-field thickness measurement of soft tissues and tissue analogs Support Protocol 1: Creating and speckling cruciform-shaped samples for mechanical testing Support Protocol 2: Creating custom gripping system to minimize sample handling.

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.

Polymer vesicles with a colloidal armor of nanoparticles.

The fabrication of polymer vesicles with a colloidal armor made from a variety of nanoparticles is demonstrated. In addition, it is shown that the armored supracolloidal structure can be postmodified through film-formation of soft polymer latex particles on the surface of the polymersome, hereby effectively wrapping the polymersome in a plastic bag, as well as through formation of a hydrogel by disintegrating an assembled polymer latex made from poly(ethyl acrylate-co-methacrylic acid) upon increasing the pH. Furthermore, ordering and packing patterns are briefly addressed with the aid of Monte Carlo simulations, including patterns observed when polymersomes are exposed to a binary mixture of colloids of different size.

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.

Population-scale single-cell RNA-seq profiling across dopaminergic neuron differentiation.

Studying the function of common genetic variants in primary human tissues and during development is challenging. To address this, we use an efficient multiplexing strategy to differentiate 215 human induced pluripotent stem cell (iPSC) lines toward a midbrain neural fate, including dopaminergic neurons, and use single-cell RNA sequencing (scRNA-seq) to profile over 1 million cells across three differentiation time points. The proportion of neurons produced by each cell line is highly reproducible and is predictable by robust molecular markers expressed in pluripotent cells. Expression quantitative trait loci (eQTL) were characterized at different stages of neuronal development and in response to rotenone-induced oxidative stress. Of these, 1,284 eQTL colocalize with known neurological trait risk loci, and 46% are not found in the Genotype-Tissue Expression (GTEx) catalog. Our study illustrates how coupling scRNA-seq with long-term iPSC differentiation enables mechanistic studies of human trait-associated genetic variants in otherwise inaccessible cell states.