Cell Polarity in Yeast.

A conserved molecular machinery centered on the Cdc42 GTPase regulates cell polarity in diverse organisms. Here we review findings from budding and fission yeasts that reveal both a conserved core polarity circuit and several adaptations that each organism exploits to fulfill the needs of its lifestyle. The core circuit involves positive feedback by local activation of Cdc42 to generate a cluster of concentrated GTP-Cdc42 at the membrane. Species-specific pathways regulate the timing of polarization during the cell cycle, as well as the location and number of polarity sites.

Negative feedback enhances robustness in the yeast polarity establishment circuit.

Many cells undergo symmetry-breaking polarization toward a randomly oriented "front" in the absence of spatial cues. In budding yeast, such polarization involves a positive feedback loop that enables amplification of stochastically arising clusters of polarity factors. Previous mathematical modeling suggested that, if more than one cluster were amplified, the clusters would compete for limiting resources and the largest would "win," explaining why yeast cells always make one and only one bud. Here, using imaging with improved spatiotemporal resolution, we show the transient coexistence of multiple clusters during polarity establishment, as predicted by the model. Unexpectedly, we also find that initial polarity factor clustering is oscillatory, revealing the presence of a negative feedback loop that disperses the factors. Mathematical modeling predicts that negative feedback would confer robustness to the polarity circuit and make the kinetics of competition between polarity factor clusters relatively insensitive to polarity factor concentration. These predictions are confirmed experimentally.

Increasing Pancreatic Cancer Incidence in Young Women in the United States: A Population-Based Time-Trend Analysis, 2001-2018.

BACKGROUND & AIMS: Previous studies have shown an increasing incidence of pancreatic cancer (PC), especially in younger women; however, this has not been externally validated. In addition, there are limited data about contributing factors to this trend. We report age and sex-specific time-trend analysis of PC age-adjusted incidence rates (aIRs) using the National Program of Cancer Registries database without Surveillance Epidemiology and End Results data. METHODS: PC aIR, mortality rates, annual percentage change, and average annual percentage change (AAPC) were calculated and assessed for parallelism and identicalness. Age-specific analyses were conducted in older (≥55 years) and younger (<55 years) adults. PC incidence based on demographics, tumor characteristics, and mortality were evaluated in younger adults. RESULTS: A total of 454,611 patients were diagnosed with PC between 2001 and 2018 with significantly increasing aIR in women (AAPC = 1.27%) and men (AAPC = 1.14%) without a difference (P = .37). Similar results were seen in older adults. However, in younger adults (53,051 cases; 42.9% women), women experienced a greater increase in aIR than men (AAPCs = 2.36%, P < .001 vs 0.62%, P = 0.62) with nonparallel trends (P < .001) and AAPC difference of 1.74% (P < .001). This AAPC difference appears to be due to rising aIR in Blacks (2.23%; P < .001), adenocarcinoma histopathologic subtype (0.89%; P = .003), and location in the head-of-pancreas (1.64%; P < .001). PC mortality was found to be unchanged in women but decreasing in counterpart men (AAPC difference = 0.54%; P = .001). CONCLUSION: Using nationwide data, covering ≈64.5% of the U.S. population, we externally validate a rapidly increasing aIR of PC in younger women. There was a big separation of the incidence trend between women and men aged 15-34 years between 2001 and 2018 (>200% difference), and it did not show slowing down.

EUS-guided coil injection therapy in the management of gastric varices: the first U.S. multicenter experience (with video).

BACKGROUND AND AIMS: Despite the significant morbidity associated with gastric variceal bleeding, there is a paucity of high-quality data regarding optimal management. EUS-guided coil injection therapy (EUS-COIL) has recently emerged as a promising endoscopic modality for the treatment of gastric varices (GV), particularly compared with traditional direct endoscopic glue injection. Although there are data on the feasibility and safety of EUS-COIL in the management of GV, these have been limited to select centers with particular expertise. The aim of this study was to report the first U.S. multicenter experience of EUS-COIL for the management of GV. METHODS: This retrospective analysis included patients with bleeding GV or GV at risk of bleeding who underwent EUS-COIL at 10 U.S. tertiary care centers between 2018 and 2022. Baseline patient and procedure-related information was obtained. EUS-COIL entailed the injection of .018 inch or .035 inch hemostatic coils using a 22-gauge or 19-gauge FNA needle. Primary outcomes were technical success (defined as successful deployment of coil into varix under EUS guidance with diminution of Doppler flow), clinical success (defined as cessation of bleeding if present and/or absence of bleeding at 30 days' postintervention), and intraprocedural and postprocedural adverse events. RESULTS: A total of 106 patients were included (mean age 60.4 ± 12.8 years; 41.5% female). The most common etiology of GV was cirrhosis (71.7%), with alcohol being the most common cause (43.4%). Overall, 71.7% presented with acute GV bleeding requiring intensive care unit stay and/or blood transfusion. The most common GV encountered were isolated GV type 1 (60.4%). A mean of 3.8 ± 3 coils were injected with a total mean length of 44.7 ± 46.1 cm. Adjunctive glue or absorbable gelatin sponge was injected in 82% of patients. Technical success and clinical success were 100% and 88.7%, respectively. Intraprocedural adverse events (pulmonary embolism and GV bleeding from FNA needle access) occurred in 2 patients (1.8%), and postprocedural adverse events occurred in 5 (4.7%), of which 3 were mild. Recurrent bleeding was observed in 15 patients (14.1%) at a mean of 32 days. Eighty percent of patients with recurrent bleeding were successfully re-treated with repeat EUS-COIL. No significant differences were observed in outcomes between high-volume (>15 cases) and low-volume (<7 cases) centers. CONCLUSIONS: This U.S. multicenter experience on EUS-COIL for GV confirms high technical and clinical success with low adverse events. No significant differences were seen between high- and low-volume centers. Repeat EUS-COIL seems to be an effective rescue option for patients with recurrent bleeding GV. Further prospective studies should compare this modality versus other interventions commonly used for GV.

Particle-based simulations reveal two positive feedback loops allow relocation and stabilization of the polarity site during yeast mating.

Many cells adjust the direction of polarized growth or migration in response to external directional cues. The yeast Saccharomyces cerevisiae orient their cell fronts (also called polarity sites) up pheromone gradients in the course of mating. However, the initial polarity site is often not oriented towards the eventual mating partner, and cells relocate the polarity site in an indecisive manner before developing a stable orientation. During this reorientation phase, the polarity site displays erratic assembly-disassembly behavior and moves around the cell cortex. The mechanisms underlying this dynamic behavior remain poorly understood. Particle-based simulations of the core polarity circuit revealed that molecular-level fluctuations are unlikely to overcome the strong positive feedback required for polarization and generate relocating polarity sites. Surprisingly, inclusion of a second pathway that promotes polarity site orientation generated relocating polarity sites with properties similar to those observed experimentally. This pathway forms a second positive feedback loop involving the recruitment of receptors to the cell membrane and couples polarity establishment to gradient sensing. This second positive feedback loop also allows cells to stabilize their polarity site once the site is aligned with the pheromone gradient.

Singularity in polarization: rewiring yeast cells to make two buds.

For budding yeast to ensure formation of only one bud, cells must polarize toward one, and only one, site. Polarity establishment involves the Rho family GTPase Cdc42, which concentrates at polarization sites via a positive feedback loop. To assess whether singularity is linked to the specific Cdc42 feedback loop, we disabled the yeast cell's endogenous amplification mechanism and synthetically rewired the cells to employ a different positive feedback loop. Rewired cells violated singularity, occasionally making two buds. Even cells that made only one bud sometimes initiated two clusters of Cdc42, but then one cluster became dominant. Mathematical modeling indicated that, given sufficient time, competition between clusters would promote singularity. In rewired cells, competition occurred slowly and sometimes failed to develop a single "winning" cluster before budding. Slowing competition in normal cells also allowed occasional formation of two buds, suggesting that singularity is enforced by rapid competition between Cdc42 clusters.

Chemotactic movement of a polarity site enables yeast cells to find their mates.

How small eukaryotic cells can interpret dynamic, noisy, and spatially complex chemical gradients to orient growth or movement is poorly understood. We address this question using Saccharomyces cerevisiae, where cells orient polarity up pheromone gradients during mating. Initial orientation is often incorrect, but polarity sites then move around the cortex in a search for partners. We find that this movement is biased by local pheromone gradients across the polarity site: that is, movement of the polarity site is chemotactic. A bottom-up computational model recapitulates this biased movement. The model reveals how even though pheromone-bound receptors do not mimic the shape of external pheromone gradients, nonlinear and stochastic effects combine to generate effective gradient tracking. This mechanism for gradient tracking may be applicable to any cell that searches for a target in a complex chemical landscape.

Novel Endoscopic Polypectomy Surveillance Technique for Fundic Gland Polyps in Familial Adenomatous Polyposis Can Improve Early Detection of Dysplasia and Gastric Cancer.

INTRODUCTION: Fundic gland polyps (FGPs) are commonly found in patients with familial adenomatous polyposis (FAP) and are considered benign. Biopsies are not routinely performed, and conventional forceps may be time-consuming and/or yield nonrepresentative histology. The purpose of this study was to evaluate the role of a novel endoscopic polypectomy surveillance (EPS), a large volume cold-snare polypectomy technique of random FGPs, in the incidence of dysplasia and gastric cancer (GC) in FAP. METHODS: This is a retrospective longitudinal cohort of patients with FAP referred to a tertiary care center for duodenal adenoma surveillance and who underwent EPS of FGPs between 2001 and 2019. Demographic, endoscopic, and clinicopathologic information was reviewed. RESULTS: Thirty-five patients with FAP were identified at initial endoscopy by the mean age of 43.4 years (±12.8). One hundred thirteen surveillance endoscopies were performed in total using EPS. Dysplasia of FGPs was present on initial esophagogastroduodenoscopy in 7 patients (20%), and 13 additional patients (46.4%) progressed to low-grade dysplasia. Three patients (15%) who subsequently had progression to GC were found to have signet ring cell cancer within the foci of FGPs through EPS. One patient presented as metastatic GC. Progression from nondysplastic FGP to low-grade dysplasia occurred over 63 months (±46.3) with further progression to GC over 34 months (±8.5). Endoscopic risk factors for cancer were polyps >10 mm in size ( P < 0.001) and carpeting of polyps ( P < 0.001). The 5-year cumulative incidence of developing dysplasia was 35.7%. DISCUSSION: We identified that the incidence of dysplasia and GC is higher than previously reported in patients with FAP. Our study used a novel EPS technique and was able to identify GC within the foci of FGPs. Upper endoscopic guidelines should include a more rigorous sampling method for FGPs, such as EPS, to optimize early detection of dysplasia and GC.

Comparison of no stent fixation, endoscopic suturing, and a novel over-the-scope clip for stent fixation in preventing migration of fully covered self-expanding metal stents: a retrospective comparative study (with video).

BACKGROUND AND AIMS: Endoscopic suturing and over-the-scope clips (OTSCs) are used to prevent migration of fully covered self-expandable metal stents (FCSEMSs). Recently, a dedicated OTSC was developed for securing FCSEMSs. Our primary aim was to compare the frequency of stent migration without stent fixation versus fixation with suturing or OTSCs, and out secondary aims were to compare clinical success, procedure duration, and adverse events. METHODS: A retrospective cohort study evaluated the outcome of stent placement throughout the entire GI tract from 2013 to 2021. Stent migration was determined as stent displacement ≥2 cm endoscopically or radiographically. Clinical success was defined as resolution of indication at follow-up. RESULTS: Four hundred thirty-three procedures were performed, 239 (55%) without fixation, 140 (32%) with suturing, and 54 (12%) with OTSCs. Stent migration rates were 62% without fixation, 57% with suturing, and 35% with OTSCs (P = .013). The median time to stent migration was 3 weeks without fixation, 5 weeks with suturing, and 6 weeks with OTSCs (P = .023). The clinical success rate was 43%. The median procedure time for OTSCs was shorter compared with suturing (42 vs 68 minutes, P = .002). Adverse event rates trended toward being lowest with OTSCs at 9% compared with 21% without fixation and 18% with suturing (P > .05). CONCLUSIONS: OTSCs for stent fixation were found to have significantly lower migration rates compared with no fixation and suturing. Moreover, OTSCs were associated with decreased overall procedure time and total costs per procedure while trending to be associated with fewer adverse events.

Ratiometric GPCR signaling enables directional sensing in yeast.

Accurate detection of extracellular chemical gradients is essential for many cellular behaviors. Gradient sensing is challenging for small cells, which can experience little difference in ligand concentrations on the up-gradient and down-gradient sides of the cell. Nevertheless, the tiny cells of the yeast Saccharomyces cerevisiae reliably decode gradients of extracellular pheromones to find their mates. By imaging the behavior of polarity factors and pheromone receptors, we quantified the accuracy of initial polarization during mating encounters. We found that cells bias the orientation of initial polarity up-gradient, even though they have unevenly distributed receptors. Uneven receptor density means that the gradient of ligand-bound receptors does not accurately reflect the external pheromone gradient. Nevertheless, yeast cells appear to avoid being misled by responding to the fraction of occupied receptors rather than simply the concentration of ligand-bound receptors. Such ratiometric sensing also serves to amplify the gradient of active G protein. However, this process is quite error-prone, and initial errors are corrected during a subsequent indecisive phase in which polarity clusters exhibit erratic mobile behavior.

Endoscopic full-thickness resection of polyps involving the appendiceal orifice: a multicenter international experience.

BACKGROUND: Endoscopic resection of lesions involving the appendiceal orifice remains a challenge. We aimed to report outcomes with the full-thickness resection device (FTRD) for the resection of appendiceal lesions and identify factors associated with the occurrence of appendicitis. METHODS: This was a retrospective study at 18 tertiary-care centers (USA 12, Canada 1, Europe 5) between November 2016 and August 2020. Consecutive patients who underwent resection of an appendiceal orifice lesion using the FTRD were included. The primary outcome was the rate of R0 resection in neoplastic lesions, defined as negative lateral and deep margins on post-resection histologic evaluation. Secondary outcomes included the rates of: technical success (en bloc resection), clinical success (technical success without need for further surgical intervention), post-resection appendicitis, and polyp recurrence. RESULTS: 66 patients (32 women; mean age 64) underwent resection of colonic lesions involving the appendiceal orifice (mean [standard deviation] size, 14.5 (6.2) mm), with 40 (61 %) being deep, extending into the appendiceal lumen. Technical success was achieved in 59/66 patients (89 %), of which, 56 were found to be neoplastic lesions on post-resection pathology. Clinical success was achieved in 53/66 (80 %). R0 resection was achieved in 52/56 (93 %). Of the 58 patients in whom EFTR was completed who had no prior history of appendectomy, appendicitis was reported in 10 (17 %), with six (60 %) requiring surgical appendectomy. Follow-up colonoscopy was completed in 41 patients, with evidence of recurrence in five (12 %). CONCLUSIONS: The FTRD is a promising non-surgical alternative for resecting appendiceal lesions, but appendicitis occurs in 1/6 cases.

A novel stochastic simulation approach enables exploration of mechanisms for regulating polarity site movement.

Cells polarize their movement or growth toward external directional cues in many different contexts. For example, budding yeast cells grow toward potential mating partners in response to pheromone gradients. Directed growth is controlled by polarity factors that assemble into clusters at the cell membrane. The clusters assemble, disassemble, and move between different regions of the membrane before eventually forming a stable polarity site directed toward the pheromone source. Pathways that regulate clustering have been identified but the molecular mechanisms that regulate cluster mobility are not well understood. To gain insight into the contribution of chemical noise to cluster behavior we simulated clustering using the reaction-diffusion master equation (RDME) framework to account for molecular-level fluctuations. RDME simulations are a computationally efficient approximation, but their results can diverge from the underlying microscopic dynamics. We implemented novel concentration-dependent rate constants that improved the accuracy of RDME-based simulations, allowing us to efficiently investigate how cluster dynamics might be regulated. Molecular noise was effective in relocating clusters when the clusters contained low numbers of limiting polarity factors, and when Cdc42, the central polarity regulator, exhibited short dwell times at the polarity site. Cluster stabilization occurred when abundances or binding rates were altered to either lengthen dwell times or increase the number of polarity molecules in the cluster. We validated key results using full 3D particle-based simulations. Understanding the mechanisms cells use to regulate the dynamics of polarity clusters should provide insights into how cells dynamically track external directional cues.

Defining the economic scope for ecosystem-based fishery management.

The emergence of ecosystem-based fisheries management (EBFM) has broadened the policy scope of fisheries management by accounting for the biological and ecological connectivity of fisheries. Less attention, however, has been given to the economic connectivity of fisheries. If fishers consider multiple fisheries when deciding where, when, and how much to fish, then management changes in one fishery can generate spillover impacts in other fisheries. Catch-share programs are a popular fisheries management framework that may be particularly prone to generating spillovers given that they typically change fishers' incentives and their subsequent actions. We use data from Alaska fisheries to examine spillovers from each of the main catch-share programs in Alaska. We evaluate changes in participation-a traditional indicator in fisheries economics-in both the catch-share and non-catch-share fisheries. Using network analysis, we also investigate whether catch-share programs change the economic connectivity of fisheries, which can have implications for the socioeconomic resilience and robustness of the ecosystem, and empirically identify the set of fisheries impacted by each Alaska catch-share program. We find that cross-fishery participation spillovers and changes in economic connectivity coincide with some, but not all, catch-share programs. Our findings suggest that economic connectivity and the potential for cross-fishery spillovers deserve serious consideration, especially when designing and evaluating EBFM policies.

The prevalence of migraine in Argentina: A reappraisal.

BACKGROUND: Argentina has one of the largest territories in the world, which spreads over a lengthy latitudinal span. Its population is mainly composed of a mixture of South American natives and the descendants of numerous waves of European immigrants. Results from a previous study suggested that the prevalence of migraine in Argentina is the lowest in the region. Here we aimed to reassess the prevalence of migraine in Argentina applying a more sensitive and specific screening tool. METHODS: We conducted a random computer assisted telephonic interview (n= 2500) using the Migraine Screen Questionnaire to evaluate the prevalence of migraine and some of its features among Argentinian adults. RESULTS: The overall prevalence of migraine was 9.5% (14% in females and 5% in males). Estimated migraine prevalence rates ranged between 6.3% and 12% across different regions. The approximated prevalence of high frequency and chronic migraine were 1.9% and 1.5% of the total population respectively. Consumption of analgesics on 10 or more days per month was reported by 18% of migraine sufferers (≈1.7% of the population). CONCLUSIONS: The prevalence of migraine in Argentina is higher than previously reported. Prevalence rates vary extensively across the territory. Specifically evaluating the determinants of these variations might be a promising avenue of research.

Comparing the Real-World Effectiveness of Competing Colonoscopy Preparations: Results of a Prospective Trial.

OBJECTIVES: National societies provide little guidance regarding which colonoscopy bowel preps are best tolerated and most effective; this reflects a lack of comparative effectiveness studies that directly evaluate the available preps in a "real-world" setting. To address this gap, we conducted a prospective, commercially unfunded comparative effectiveness study of currently available bowel preps and measured their impact on bowel cleansing. METHODS: We included patients aged ≥18 years, who presented for an outpatient colonoscopy at a large medical center serving more than 70 academic and community-based endoscopists who are free to prescribe the bowel prep of their choice. The primary outcome was bowel cleansing quality as measured by the Boston Bowel Preparation Scale. We performed regression models with random effects on the outcomes to adjust for confounding. RESULTS: Approximately 4,339 colonoscopies were performed by 75 endoscopists. Magnesium citrate, MiraLAX with Gatorade, MoviPrep, OsmoPrep, Prepopik/Clenpiq, and Suprep all had significantly higher prep tolerability compared with GoLYTELY (all P < 0.05). For bowel cleansing, Suprep (7.28 ± 1.66; P < 0.001), MoviPrep (7.11 ± 1.62; P = 0.004), and MiraLAX with Gatorade (7.09 ± 1.64; P < 0.001) had higher total Boston Bowel Preparation Scale scores compared with GoLYTELY (6.67 ± 1.87); there were no significant differences among the remaining preps. Split-prep dosing was associated with better cleansing; however, men, opioid and tricyclic antidepressent users, and patients with diabetes and cirrhosis had worse cleansing (all P < 0.05). CONCLUSIONS: In this prospective, real-world comparative effectiveness study of available bowel preps, we found that MiraLAX with Gatorade, MoviPrep, and Suprep were prospectively associated with superior tolerability and bowel cleansing.

Principles that govern competition or co-existence in Rho-GTPase driven polarization.

Rho-GTPases are master regulators of polarity establishment and cell morphology. Positive feedback enables concentration of Rho-GTPases into clusters at the cell cortex, from where they regulate the cytoskeleton. Different cell types reproducibly generate either one (e.g. the front of a migrating cell) or several clusters (e.g. the multiple dendrites of a neuron), but the mechanistic basis for unipolar or multipolar outcomes is unclear. The design principles of Rho-GTPase circuits are captured by two-component reaction-diffusion models based on conserved aspects of Rho-GTPase biochemistry. Some such models display rapid winner-takes-all competition between clusters, yielding a unipolar outcome. Other models allow prolonged co-existence of clusters. We investigate the behavior of a simple class of models and show that while the timescale of competition varies enormously depending on model parameters, a single factor explains a large majority of this variation. The dominant factor concerns the degree to which the maximal active GTPase concentration in a cluster approaches a "saturation point" determined by model parameters. We suggest that both saturation and the effect of saturation on competition reflect fundamental properties of the Rho-GTPase polarity machinery, regardless of the specific feedback mechanism, which predict whether the system will generate unipolar or multipolar outcomes.

Cost Effectiveness of Biomarker Tests for Irritable Bowel Syndrome With Diarrhea: A Framework for Payers.

BACKGROUND & AIMS: Diagnosis of diarrhea-predominant irritable bowel syndrome (IBS-D) relies on the Rome IV symptom-based criteria, which are imperfect for separating functional vs organic disease. Biomarker tests for IBS-D might be added to symptom data to allow clinicians to make more accurate and precise diagnoses in a cost-effective manner. We tested the economic consequences of using a range of hypothetical IBS-D biomarkers, and explored at what cost and level of accuracy a biomarker becomes cost effective. We produced a framework for payers to evaluate the return on an investment of implementing IBS-D biomarkers of varying accuracy and cost. METHODS: We used decision analysis software to evaluate a hypothetical cohort of patients who met Rome IV criteria for IBS-D. We conducted cost-utility and budget impact analyses of 2 competing approaches: usual care or an IBS biomarker-based diagnostic approach. Patients in the usual care group received empiric IBS treatment; non-responders received additional diagnostic tests for organic disease. In the group evaluated with a biomarker test, those with a positive result received IBS treatment before additional diagnostic analyses, whereas patients with a negative result underwent upfront diagnostic testing. Outcomes were incremental cost per quality-adjusted life year gained (third-party payer perspective) and incremental per-member per-month cost. RESULTS: In the base-case analysis, using a willingness-to-pay threshold of $100,000/quality-adjusted life year, we found that biomarkers are not cost effective when the biomarker test costs more than $846, even if the test is 100% accurate in detecting IBS-D. In probabilistic analysis using 1,000 simulations, most trials (75% or more) show that the biomarker-based diagnostic approach is cost effective above the following accuracy thresholds: a $100 biomarker test with 51% accuracy, a $200 test with 57% accuracy, a $300 test with 63% accuracy, a $400 test with 69% accuracy, a $500 test with 76% accuracy, a $600 test with 82% accuracy, a $700 test with 89% accuracy, and a $800 test with 94% accuracy. CONCLUSIONS: In decision analysis of a hypothetical cohort of patients who met Rome IV criteria for IBS-D, we identified cost and accuracy thresholds that can guide investigators and payers as they develop, validate, price, and/or reimburse IBS-D biomarker tests for use in everyday clinical practice.

A randomized, controlled study to investigate the efficacy and safety of a topical gentamicin-collagen sponge in combination with systemic antibiotic therapy in diabetic patients with a moderate or severe foot ulcer infection.

BACKGROUND: An adjunctive topical therapy with gentamicin-sponges to systemic antibiotic therapy might improve the healing of infected diabetic foot ulcers (DFUI). METHODS: Single-center, investigator-blinded pilot study, randomizing (1:1) the gentamicin-sponge with systemic antibiotic versus systemic antibiotics alone for patients with DFUI. RESULTS: We included 88 DFUI episodes with 43 patients in the gentamicin-sponge arm and 45 in the control arm. Overall, 64 (64/88; 73%) witnessed total clinical cure, 13 (15%) significant improvement, and 46 (52%) showed total eradication of all pathogens at the final visit. Regarding final clinical cure, there was no difference in favour of the gentamicin-sponges (26/45 vs. 31/43; p = 0.16). However, the gentamicin-sponge arm tended to a more rapid healing. In multivariate analysis adjusting for the case-mix, the variable "gentamicin-sponge" was not significantly associated with "cure and improvement". Gentamicin-sponges were very well tolerated, without any attributed adverse events. CONCLUSIONS: The gentamicin-sponge was very well tolerated, but did not significantly influence overall cure. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01951768 ). Date 2 April 2013.

How do cells know what shape they are?

Studies on a yeast cell cycle checkpoint that can delay mitosis depending on whether cells have built a bud have identified a "sensor" that seems to recognize the organization of filament-forming septin proteins. Innovative work applying correlative light and platinum replica electron microscopy suggests that the informative septin organization involves parallel alignment of septin filaments, and another striking study shows that septin filaments prefer to populate membranes that have positive micron-scale curvature. Together, these findings suggest a model for how cells may monitor aspects of their own shape to influence cell behavior.