Nonhomologous tails direct heteroduplex rejection and mismatch correction during single-strand annealing in Saccharomyces cerevisiae.

Single-strand annealing (SSA) is initiated when a double strand break (DSB) occurs between two flanking repeated sequences, resulting in a deletion that leaves a single copy of the repeat. We studied budding yeast strains carrying two 200-bp URA3 sequences separated by 2.6 kb of spacer DNA (phage lambda) in which a site-specific DSB can be created by HO or Cas9 endonucleases. Repeat-mediated deletion requires removal of long 3'-ended single-stranded tails (flaps) by Rad1-Rad10 with the assistance of Msh2-Msh3, Saw1 and Slx4. A natural 3% divergence of unequally spaced heterologies between these repeats (designated F and A) causes a significant reduction in the frequency of SSA repair. This decrease is caused by heteroduplex rejection in which mismatches (MMs) in the annealed intermediate are recognized by the MutS (Msh2 and Msh6) components of the MM repair (MMR) pathway coupled to unwinding of the duplex by the Sgs1-Rmi1-Top3 helicase. MutL homologs, Mlh1-Pms1 (MutL), are not required for rejection but play their expected role in mismatch correction. Remarkably, heteroduplex rejection is very low in strains where the divergent repeats were immediately adjacent (Tailless strains) and the DSB was induced by Cas9. These results suggest that the presence of nonhomologous tails strongly stimulates heteroduplex rejection in SSA. DNA sequencing analysis of SSA products from the FA Tailed strain showed a gradient of correction favoring the sequence opposite each 3' end of the annealed strand. Mismatches located in the center of the repair intermediate were corrected by Msh2-Msh6 mediated mismatch correction, while correction of MMs at the extremity of the SSA intermediate often appears to use a different mechanism, possibly by 3' nonhomologous tail removal that includes part of the homologous sequence. In contrast, in FA Tailless strains there was a uniform repair of the MMs across the repeat. A distinctive pattern of correction was found in the absence of MSH2, in both Tailed and Tailless strains, different from the spectrum seen in a msh3Δ msh6Δ double mutant. Previous work has shown that SSA is Rad51-independent but dependent on the strand annealing activity of Rad52. However Rad52 becomes dispensable in a Tailless construct where the DSB is induced by Cas9 or in transformation of a plasmid where SSA occurs in the absence of nonhomologous tails.

Drought resistance strategies in minor millets: a review.

MAIN CONCLUSION: The review discusses growth and drought-response mechanisms in minor millets under three themes: drought escape, drought avoidance and drought tolerance. Drought is one of the most prominent abiotic stresses impacting plant growth, performance, and productivity. In the context of climate change, the prevalence and severity of drought is expected to increase in many agricultural regions worldwide. Millets (coarse grains) are a group of small-seeded grasses cultivated in arid and semi-arid regions throughout the world and are an important source of food and feed for humans and livestock. Although minor millets, i.e., foxtail millet, finger millet, proso millet, barnyard millet, kodo millet and little millet are generally hardier and more drought-resistant than cereals and major millets (sorghum and pearl millet), understanding their responses, processes and strategies in response to drought is more limited. Here, we review drought resistance strategies in minor millets under three themes: drought escape (e.g., short crop cycle, short vegetative period, developmental plasticity and remobilization of assimilates), drought avoidance (e.g., root traits for better water absorption and leaf traits to control water loss), and drought tolerance (e.g., osmotic adjustment, maintenance of photosynthetic ability and antioxidant potential). Data from 'omics' studies are summarized to provide an overview of the molecular mechanisms important in drought tolerance. In addition, the final section highlights knowledge gaps and challenges to improving minor millets. This review is intended to enhance major cereals and millet per se in light of climate-related increases in aridity.

The Aesthetic Surgery Education and Research Foundation (ASERF): A 30-Year Retrospective Analysis.

Federal government research grants provide limited funding to plastic surgeon-scientists, with reconstructive research taking precedence over aesthetic research. The Aesthetic Surgery Education and Research Foundation (ASERF) is a nonprofit, 501(c)(3) organization that seeks to support innovative, diverse research endeavors within aesthetic surgery. A total of 130 ASERF-funded studies and 32 non-funded applications from 1992 to 2022 were reviewed. Kruskal Wallis, Fisher's exact, and chi-squared tests were utilized to assess the potential relationship between self-identified gender, practice setting, geographical location, and study type with individual grant amounts and grant funding decision. Although significant differences were observed between male and female grant recipient h-indices (P < .05), there were no differences in the amount of funding they received (P > .05). Grant amounts were also consistent between study types as well as principal investigator practice settings and geographical locations (P > .05). The subanalysis revealed that the practice setting of the primary investigator (PI) was the only variable to exhibit a significant association with the decision to award funding (P < .05). Further, of the 61 applicants between 2017 and 2022, only 2 PIs self-identified as female. ASERF serves as an excellent funding source for global aesthetic surgery. To promote further research diversification, increased emphasis should be placed on recruiting applicants from outside academia and those who identify as female or gender nonbinary.

Activated Platelets Mediate Monocyte Killing of Klebsiella pneumoniae.

Platelets are known for essential activities in hemostasis and for their important contribution to protection against infectious pathogens. Klebsiella pneumoniae is an opportunistic pathogen widely known to cause nosocomial infections. Recently, hypervirulent strains of K. pneumoniae have been emerging, which can cause severe infections in immunocompetent individuals. Combined with the increase in antibiotic resistance, it is important to understand how K. pneumoniae affects components of the immune system. We studied the interactions of human platelets with several K. pneumoniae strains (the wild type encapsulated strain, and a nonencapsulated mutant). Thrombin-stimulated whole human and mouse blood significantly inhibited bacterial growth compared to unstimulated whole blood. Furthermore, we investigated the effect of K. pneumoniae on platelet activation. Both strains induced significant increase in activation of both unstimulated and thrombin-stimulated human platelets. Additionally, only the nonencapsulated mutant increased aggregation of platelets in response to ADP. K. pneumoniae killing assays were then performed with washed platelets in the presence or absence of thrombin. Surprisingly, washed platelets failed to exhibit any effects on the growth of K. pneumoniae. We further explored the impact of platelets on monocyte-mediated killing of K. pneumoniae. Importantly, we found that activated platelets significantly enhanced monocyte-mediated killing of K. pneumoniae. This effect was likely due to the formation of platelet-monocyte aggregates in blood upon thrombin stimulation. Overall, this study highlights the role of platelets in mediating a protective response against K. pneumoniae and reinforces the importance of platelets in modulating leukocyte behavior.

Understanding the Pain Management Landscape Within the US Bleeding Disorder Community: A Multi-Center Survey.

OBJECTIVES: Pain is a known complication in persons with hemophilia (PWH) as a result of muscle and joint bleeding. Little is known regarding national Hemophilia Treatment Center (HTC) practice patterns related to pain management. The aim of this study was to: 1) Describe pain management practice patterns of HTC providers, 2) Identify gaps and areas of alignment with the CDC pain guidelines, and 3) Address educational opportunities for pain management. This survey is the first extensive description of multidisciplinary practice patterns of pain management for PWH. METHODS: This descriptive study involved physicians, nurse practitioners, nurses, physical therapists, and social workers from federally funded Hemophilia Treatment Centers (HTC) eligible to complete an online survey exploring pain management practice patterns within the CDC pain guidelines. RESULTS: Results of this survey shed light on areas of strength and cohesiveness between HTC providers, including the following: dedication to effective pain management, utilization of non-pharmacological pain options, trial of non-opioid medications first before opioids, maintaining follow-up with patients after opioid prescription initiation, recognizing and utilizing clinically important findings before prescribing opioids, and counseling their patients regarding potential risk factors. CONCLUSIONS: There remain opportunities to incorporate into clinical practice consistent use of tools such as formal screening questionnaires, opioid use agreements, written measurable goals, ongoing prescription monitoring, and written plans for discontinuation of opioid therapy. These results provide opportunities for improvement in education of HTC team members thus optimizing pain management in persons with bleeding disorders.

Myogenic Cell Expression of Intercellular Adhesion Molecule-1 Contributes to Muscle Regeneration after Injury.

This study investigated intercellular adhesion molecule-1 (ICAM-1), a membrane protein that mediates cell-to-cell adhesion and communication, as a mechanism through which the inflammatory response facilitates muscle regeneration after injury. Toxin-induced muscle injury to tibialis anterior muscles of wild-type mice caused ICAM-1 to be expressed by a population of satellite cells/myoblasts and myofibers. Myogenic cell expression of ICAM-1 contributed to the restoration of muscle structure after injury, as regenerating myofibers were more abundant and myofiber size was larger for wild-type compared with Icam1-/- mice during 28 days of recovery. Contrastingly, restoration of muscle function after injury was similar between the genotypes. ICAM-1 facilitated the restoration of muscle structure after injury through mechanisms involving the regulation of myofiber branching, protein synthesis, and the organization of nuclei within myofibers after myogenic cell fusion. These findings provide support for a paradigm in which ICAM-1 expressed by myogenic cells after muscle injury augments their adhesive and fusogenic properties, which, in turn, facilitates regenerative and hypertrophic processes that restore structure to injured muscle.

Value of treatment by comprehensive stroke services for the reduction of critical gaps in acute stroke care in Europe.

Stroke is the second leading cause of death and dependency in Europe and costs the European Union more than €30bn, yet significant gaps in the patient pathway remain and the cost-effectiveness of comprehensive stroke care to meet these needs is unknown. The European Brain Council Value of Treatment Initiative combined patient representatives, stroke experts, neurological societies and literature review to identify unmet needs in the patient pathway according to Rotterdam methodology. The cost-effectiveness of comprehensive stroke services was determined by a Markov model, using UK cost data as an exemplar and efficacy data for prevention of death and dependency from published systematic reviews and trials, expressing effectiveness as quality-adjusted life-years (QALYs). Model outcomes included total costs, total QALYs, incremental costs, incremental QALYs and the incremental cost-effectiveness ratio (ICER). Key unmet needs in the stroke patient pathway included inadequate treatment of atrial fibrillation (AF), access to neurorehabilitation and implementation of comprehensive stroke services. In the Markov model, full implementation of comprehensive stroke services was associated with a 9.8% absolute reduction in risk of death of dependency, at an intervention cost of £9566 versus £6640 for standard care, and long-term care costs of £35 169 per 5.1251 QALYS vs. £32 347.40 per 4.5853 QALYs, resulting in an ICER of £5227.89. Results were robust in one-way and probabilistic sensitivity analyses. Implementation of comprehensive stroke services is a cost-effective approach to meet unmet needs in the stroke patient pathway, to improve acute stroke care and support better treatment of AF and access to neurorehabilitation.

Observation of antiferromagnetic correlations in the Hubbard model with ultracold atoms.

Ultracold atoms in optical lattices have great potential to contribute to a better understanding of some of the most important issues in many-body physics, such as high-temperature superconductivity. The Hubbard model--a simplified representation of fermions moving on a periodic lattice--is thought to describe the essential details of copper oxide superconductivity. This model describes many of the features shared by the copper oxides, including an interaction-driven Mott insulating state and an antiferromagnetic (AFM) state. Optical lattices filled with a two-spin-component Fermi gas of ultracold atoms can faithfully realize the Hubbard model with readily tunable parameters, and thus provide a platform for the systematic exploration of its phase diagram. Realization of strongly correlated phases, however, has been hindered by the need to cool the atoms to temperatures as low as the magnetic exchange energy, and also by the lack of reliable thermometry. Here we demonstrate spin-sensitive Bragg scattering of light to measure AFM spin correlations in a realization of the three-dimensional Hubbard model at temperatures down to 1.4 times that of the AFM phase transition. This temperature regime is beyond the range of validity of a simple high-temperature series expansion, which brings our experiment close to the limit of the capabilities of current numerical techniques, particularly at metallic densities. We reach these low temperatures using a compensated optical lattice technique, in which the confinement of each lattice beam is compensated by a blue-detuned laser beam. The temperature of the atoms in the lattice is deduced by comparing the light scattering to determinant quantum Monte Carlo simulations and numerical linked-cluster expansion calculations. Further refinement of the compensated lattice may produce even lower temperatures which, along with light scattering thermometry, would open avenues for producing and characterizing other novel quantum states of matter, such as the pseudogap regime and correlated metallic states of the two-dimensional Hubbard model.

Paradoxical Temporal Enlargement: An Expansion of Superficial Temporal Fat Pad Following Interfacial Technique for Pterional Craniotomy.

OBJECTIVE: Contour irregularities in the temporal region have been reported previously after procedures involving temporal dissection. In this study, we report paradoxical temporal enlargement (PTE) following interfascial pterional craniotomy. METHODS: A retrospective review of patients who underwent a unilateral transcranial procedure with frontotemporal approach at our institution between September 2013 and December 2017 was performed. Patients with a previous craniotomy or bilateral craniotomy were excluded. Radiological imaging series including computed tomography and magnetic resonance imaging were utilized to calculate temporal soft tissue volumes both preoperatively and postoperatively by using advanced software technology. Relative soft tissue volume differences between the operative side and the contralateral side were calculated at different time-points including preoperative, 3-months follow-up (3M), 12-months (12M) follow-up, and the last follow-up (LFU, over 1-year). RESULTS: Forty-three patients were included. Mean age was 52.7 ± 4.5 years. Mean follow-up was 27.9 ± 15.8 months. Significant changes of temporal fat pad relative-volume difference were observed between the preoperative and the corresponding 3M (t [82] = -2.8865, P = 0.0050); 12M (t [77] = -4.4321, P < 0.0001), and LFU (t [74] = -4.9862, P < 0.0001) postoperative time points. No significant change of the temporalis muscle was observed between the preoperative and the corresponding 3M (P = 0.3629), 12M (P = 0.1553), or LFU (P = 0.0715). Soft tissue volume showed a significant increase on the operative side between the preoperative and the corresponding LFU (t [74] = -2.5866, P =  0.0117). CONCLUSIONS: Paradoxical temporal enlargement with more than 10% volumetric change was observed in 24% of the patients at their LFU (>1-year). This change was not due to temporalis muscle changes. Paradoxical temporal enlargement was due to hypertrophy of the superficial temporal fat pad. Before surgical correction of postoperative temporal contour changes, it is important to obtain imaging and characterize the etiology of the deformity.

Heads Up Play: Acute Assessment and Management of Basketball-Related Craniofacial Injuries by On-Court Personnel.

INTRODUCTION: With a following of over 825 million people, basketball currently ranks amongst the world's most popular sports. Despite a number of concussion awareness and player safety protocols that have been implemented at the professional level of organized play, a standardized, layperson-friendly algorithm for the acute management of basketball-related craniofacial injuries does not appear to presently exist. METHODS: This 10-year retrospective cohort study was conducted using the National Electronic Injury Surveillance System database to examine basketball-related craniofacial injuries from 2010 to 2019. Within the National Electronic Injury Surveillance System dataset, factors including patient age, gender, diagnosis, injury type, and injury location were included in our analysis. RESULTS: Overall, 22,529 basketball-related craniofacial injuries occurred between 2010 and 2019 in players ages 5 to 49 years old. Adolescent (12-18-year-old) and young adult (19-34-year-old) age groups had the highest incidence of craniofacial injuries. The adolescent cohort experienced a significantly greater proportion of concussions and lower proportion of both facial lacerations and fractures compared with the within group null hypothesis of equal proportions (P < 0.05). The young adult cohort experienced a significantly greater proportion of facial lacerations and fractures and lower proportion of concussions, contusions/abrasions, hematomas, and internal injuries compared to this cohort's null hypothesis (P < 0.05). Males experienced a significantly greater proportion of fractures, lacerations, and dental injuries and lower proportion of concussions, contusions/abrasions, and internal injuries compared to the hypothesized equality of proportions (P < 0.05). Females experienced a significantly greater proportion of concussions, contusions/abrasions, and internal injuries and lower proportion of fractures, lacerations, and dental injuries compared to the hypothesized equality of proportions (P < 0.05). CONCLUSIONS: Although several steps have already been taken at the professional level to try to promote player safety, particularly with concussion protocols and prevention of lower extremity injuries, there remains a paucity of resources to guide management of other types of acute craniofacial injury. The role of layperson-friendly educational interventions remains intriguing as a potential means of improving outcomes regardless of socioeconomic status or health literacy. Additional studies still need to be completed to determine efficacy and best future direction.

Rolling With the Punches: A National Electronic Injury Surveillance System Database Study of Craniofacial Injuries in Boxing.

INTRODUCTION: Boxing is a popular combat sport in which competitors may sustain high impact blows to the face. For this reason, they are at high risk for craniofacial injuries; however, data on facial injuries specific to boxing remains sparse. Studies on safety measures, such as headgear, to prevent such injuries in boxing have been inconclusive. Boxing is popular with a wide audience. However, there is no consensus on safety measures across different populations involved in boxing due to lack of data. The objective of this study is to characterize the demography and incidence of injury types of patients presenting to emergency departments with boxing-related craniofacial injuries on a national scale in order to facilitate the establishment of evidence-based safety guidelines for prevention of boxing-related injuries. METHODS: The National Electronic Injury Surveillance System database was searched for boxing-related craniofacial injuries from the last 10 years (2010-2019). Injuries involving boxing were isolated and organized into 5-year age groups. Information on demographics and injury type was extracted from the National Electronic Injury Surveillance System database. Statistical analysis was performed between different age and gender groups. RESULTS: A total of 749 boxing-related craniofacial injuries treated in US emergency departments between 2010 and 2019 were recorded. The 19 to 34-year-old age group had the highest number of cases (54%), followed by the 12 to 18-year-old age group (31%). The most common injury types within both of these age groups were concussions and lacerations. This difference was found to be significant when compared to other craniofacial injury types (P < 0.05). The majority of athletes in these age groups were male (93% and 91%, respectively). Analysis of sex differences demonstrated concussions were more common in females compared to other injury types, whereas lacerations in males were more common compared to other injury types; these differences were found to be significant (P < 0.05). CONCLUSIONS: The high incidence of boxing-related craniofacial injuries such as concussions and lacerations incurred in young adults (19-34 years) and adolescents (12-18 years) indicate that protective measures such as community-based safety interventions and revised guidelines for protective equipment may be indicated in these groups to protect against craniofacial injuries such as lacerations and concussions. Further studies are required to develop algorithms for management of boxing-related craniofacial injuries and to evaluate the safety and efficacy of protective equipment such as boxing headgear on concussions.

Safe at the Plate: Acute Assessment and Management of Baseball-Related Craniofacial Injuries by On-Field Personnel.

INTRODUCTION: Long regarded as "America's Past Time", over 8.6 million children partake in organized and recreational baseball. Although improved equipment has reduced contemporary injury rates, nearly half of pediatric baseball injuries requiring hospitalization are due to craniofacial trauma. Sideline personnel at the youth levels, often without advanced medical training, frequently act as first-responders in instances of acute craniofacial injury. METHODS: An IRB-approved survey was distributed nationally to target field personnel working at youth, high school, collegiate, and professional baseball levels. Survey items included: comfort in assessing subtypes of acute craniofacial trauma (loss of consciousness (LOC), skull injury, orbital injury, nasal injury, and dental injury) via Likert scale, years of medical training, presence of an emergency action plan (EAP), and access to higher level care from emergency medical services (EMS) or a nearby hospital. RESULTS: When comparing the amateur and professional cohorts, the respondents from professional teams were significantly more confident in assessing LOC (P = 0.001), skull injury (P < 0.001), orbital injury (P < 0.001), nasal injury (P < 0.001), and dental injury (P < 0.001). The professional teams had significantly more years of first aid training (P < 0.0001) and were significantly more likely to have an EAP (P < 0.0001). Professional teams also had a significantly higher average of reported craniofacial incidents (P = 0.0279). CONCLUSION: The authors identified a significant disparity in comfort level between amateur and professional baseball field personnel for identifying and managing acute craniofacial trauma. Based on these findings, the authors were able to develop a rudimentary tool for on-field personnel to effectively assess and manage craniofacial injuries.

Skating on Thin Ice: Craniofacial Injuries in Amateur Ice Hockey.

INTRODUCTION: Hockey is a sport of high speeds, projectiles, and slick surfaces. A scenario is ripe for craniofacial injuries. Annually, over 1 million Americans, with many more abroad participate in organized hockey. This number continues to grow at youth, amateur and professional levels. Following the characterization of groups with the highest incidence of hockey-related craniofacial injuries, our goal is to propose guidelines for the acute management of hockey-related craniofacial injuries in amateur settings. METHODS: This study follows a 10-year retrospective cohort design, examining hockey-related craniofacial injury data derived from the National Electronic Injury Surveillance System database. Within the NEISS data, patients were stratified by age, gender, and ethnicity to allow for analysis and comparison between groups. RESULTS: Sample data consisted of 2,544 hockey-related craniofacial injuries treated in US emergency departments between 2010 and 2019. Majority of the injuries included in this analysis involved patients within the 12-18-year-old age group (53.8%). Of the diagnoses, concussion was the most frequent hockey-related craniofacial injury (39.9%). Dental injuries represented the least (1%). In the 12 to 18 age group, the diagnoses concussion, fracture, and laceration differed significantly from the null hypothesis of equality of proportions across all injury types (P < 0.05). Similarly, within the 19 to 34 age group, the diagnoses of concussion, fracture, laceration, and internal injury differed significantly from the null hypothesis of assumed equality of proportion (P < 0.05). CONCLUSIONS: High incidence of hockey-related craniofacial injury among patients 12 to 18 years of age signals a need for continued interventions targeted towards this age group. Increased sideline personnel training and education, as well as promoting a stricter adherence to established guidelines are integral parts of a greater strategy towards reducing injury incidence. Working towards reducing injuries and making participation in hockey safer, should be a goal as the sport continues to experience a historic rise in interest and participation.

Kick Start to an Epidemiological Report of Soccer-Related Craniofacial Trauma Analysis.

INTRODUCTION: Soccer is a global sport played by millions annually with an increasing popularity in the United States. Game is played by a wide range of participants from all ages and levels of competition. This scenario leads to a potential disparity in the injury profile based on quantifiable demographics. As the game continues to grow, injury detection and side-line assessment must change as well. METHODS: Utilizing a national injury database, a retrospective cohort study was conducted using 10 years of data collected from randomly selected emergency departments across the United States. Patient demographics, injury sites, and diagnosis were recorded. Diagnoses examined included concussion, contusion or abrasion, dental injury, fracture, hematoma, hemorrhage, internal injury, and laceration. RESULTS: Highest percentage of craniofacial injuries was observed in soccer players between the ages of 12 and 18. In ages 6 to 11 the most common injuries were contusions and dental injuries, with a significantly low number of fractures. Within the age group of 12 to 18 the highest percentage of injuries was concussions. Finally, the highest percentage of injury in the ages of 19 to 34 were fractures and lacerations. DISCUSSION: There is a shift in injury profile as the age of soccer players increases and the level of play becomes faster-paced. In youth players, there is a higher percentage of soft tissue injury. Older players are more likely to suffer a higher degree of injury including fractures, concussions, and lacerations. This suggests a great utility for a layperson-friendly educational intervention initiative applicable to all demographics for the sport of soccer.

Impact of Digestive Inflammatory Environment and Genipin Crosslinking on Immunomodulatory Capacity of Injectable Musculoskeletal Tissue Scaffold.

The paracrine and autocrine processes of the host response play an integral role in the success of scaffold-based tissue regeneration. Recently, the immunomodulatory scaffolds have received huge attention for modulating inflammation around the host tissue through releasing anti-inflammatory cytokine. However, controlling the inflammation and providing a sustained release of anti-inflammatory cytokine from the scaffold in the digestive inflammatory environment are predicated upon a comprehensive understanding of three fundamental questions. (1) How does the release rate of cytokine from the scaffold change in the digestive inflammatory environment? (2) Can we prevent the premature scaffold degradation and burst release of the loaded cytokine in the digestive inflammatory environment? (3) How does the scaffold degradation prevention technique affect the immunomodulatory capacity of the scaffold? This study investigated the impacts of the digestive inflammatory environment on scaffold degradation and how pre-mature degradation can be prevented using genipin crosslinking and how genipin crosslinking affects the interleukin-4 (IL-4) release from the scaffold and differentiation of naïve macrophages (M0). Our results demonstrated that the digestive inflammatory environment (DIE) attenuates protein retention within the scaffold. Over 14 days, the encapsulated protein released 46% more in DIE than in phosphate buffer saline (PBS), which was improved through genipin crosslinking. We have identified the 0.5 (w/v) genipin concentration as an optimal concentration for improved IL-4 released from the scaffold, cell viability, mechanical strength, and scaffold porosity, and immunomodulation studies. The IL-4 released from the injectable scaffold could differentiate naïve macrophages to an anti-inflammatory (M2) lineage; however, upon genipin crosslinking, the immunomodulatory capacity of the scaffold diminished significantly, and pro-inflammatory markers were expressed dominantly.

Stepping Up to the Plate(let) against Candida albicans.

Candida albicans is a pervasive commensal fungus that is the most common pathogen responsible for invasive fungal infection (IFI). With incidence of IFI on the rise due to increasing susceptible populations, it is imperative that we investigate how Candida albicans interacts with blood components. When stimulating either human or mouse whole blood with thrombin, we saw a significant decrease in C. albicans survival. We then repeated Candida killing assays with thrombin-stimulated or unstimulated washed platelets and saw a similar decrease in CFU. To investigate whether killing was mediated through surface components or releasable products, platelets were pretreated with an inhibitor of actin polymerization (cytochalasin D [CytoD]). CytoD was able to abrogate C. albicans killing. Moreover, dilution of releasates from thrombin-stimulated platelets showed that the toxicity of the releasates on C. albicans is concentration dependent. We then investigated C. albicans actions on platelet activation, granule release, and aggregation. While C. albicans does not appear to affect alpha or dense granule release, C. albicans exerts a significant attenuation of platelet aggregation to multiple agonists. These results illustrate for the first time that platelets can directly kill C. albicans through release of their granular contents. Additionally, C. albicans can also exert inhibitory effects on platelet aggregation.

Collisional Loss of One-Dimensional Fermions Near a p-Wave Feshbach Resonance.

We study collisional loss of a quasi-one-dimensional spin-polarized Fermi gas near a p-wave Feshbach resonance in ultracold ^{6}Li atoms. We measure the location of the p-wave resonance in quasi-1D and observe a confinement-induced shift and broadening. We find that the three-body loss coefficient L_{3} as a function of the quasi-1D confinement has little dependence on confinement strength. We also analyze the atom loss with a two-step cascade three-body loss model in which weakly bound dimers are formed prior to their loss arising from atom-dimer collisions. Our data are consistent with this model. We also find a possible suppression in the rate of dimer relaxation with strong quasi-1D confinement. We discuss the implications of these measurements for observing p-wave pairing in quasi-1D.

Emergence and Disruption of Spin-Charge Separation in One-Dimensional Repulsive Fermions.

At low temperature, collective excitations of one-dimensional (1D) interacting fermions exhibit spin-charge separation, a unique feature predicted by the Tomonaga-Luttinger liquid (TLL) theory, but a rigorous understanding remains challenging. Using the thermodynamic Bethe ansatz (TBA) formalism, we analytically derive universal properties of a 1D repulsive spin-1/2 Fermi gas with arbitrary interaction strength. We show how spin-charge separation emerges from the exact TBA formalism, and how it is disrupted by the interplay between the two degrees of freedom that brings us beyond the TLL paradigm. Based on the exact low-lying excitation spectra, we further evaluate the spin and charge dynamical structure factors (DSFs). The peaks of the DSFs exhibit distinguishable propagating velocities of spin and charge as functions of interaction strength, which can be observed by Bragg spectroscopy with ultracold atoms.

Quantum Fluctuations of the Center of Mass and Relative Parameters of Nonlinear Schrödinger Breathers.

We study quantum fluctuations of macroscopic parameters of a nonlinear Schrödinger breather-a nonlinear superposition of two solitons, which can be created by the application of a fourfold quench of the scattering length to the fundamental soliton in a self-attractive quasi-one-dimensional Bose gas. The fluctuations are analyzed in the framework of the Bogoliubov approach in the limit of a large number of atoms N, using two models of the vacuum state: white noise and correlated noise. The latter model, closer to the ab initio setting by construction, leads to a reasonable agreement, within 20% accuracy, with fluctuations of the relative velocity of constituent solitons obtained from the exact Bethe-ansatz results [Phys. Rev. Lett. 119, 220401 (2017)PRLTAO0031-900710.1103/PhysRevLett.119.220401] in the opposite low-N limit (for N≤23). We thus confirm, for macroscopic N, the breather dissociation time to be within the limits of current cold-atom experiments. Fluctuations of soliton masses, phases, and positions are also evaluated and may have experimental implications.

Quantitative blood flow evaluation of vasodilation-stress compared with dobutamine-stress in patients with end-stage liver disease using 82Rb PET/CT.

BACKGROUND: Our aim was to determine if end-stage liver disease (ESLD) is associated with an attenuated response to vasodilator-stress or dobutamine-stress using 82Rb-PET MPI with blood flow quantification. METHODS AND RESULTS: Pre-liver transplant patients who had a normal dipyridamole-stress (n = 27) or dobutamine-stress (n = 26) 82Rb PET/CT MPI study with no identifiable coronary artery calcium were identified retrospectively and compared to a prospectively identified low-risk of liver disease dipyridamole-stress control group (n = 20). The dipyridamole-stress liver disease group had a lower myocardial flow reserve (MFR) (1.89 ± 0.79) than the control group (2.79 ± 0.96, P < .05). The dobutamine-stress group had a higher MFR than both other groups (3.69 ± 1.49, P < .05). A moderate negative correlation between MELD score and MFR was demonstrated for the dipyridamole-stress liver disease group (r = - 0.473, P < .05). This correlation was not observed for the dobutamine-stress liver disease group (r = - 0.253, P = .21). The liver failure group as a whole (n = 53) had a higher resting myocardial blood flow (0.97 ± 0.33 mL/min/g) than the control group (0.82 ± 0.26, P < .05). CONCLUSION: Dipyridamole demonstrates an attenuated vasodilatory response in ESLD patients compared to a non-ESLD control group related to higher resting blood flow and comparatively reduced stress blood flow. Dobutamine does not demonstrate this effect implying it may be the preferred pharmacologic MPI stress agent for ESLD patients.