Risk-scoring system predicting need for hospital-specific interventional care after peroral endoscopic myotomy.

OBJECTIVES: Early identification of patients needing hospital-specific interventional care (HIC) following endoscopic treatment is valuable for optimizing postoperative hospital stays. We aimed to develop and validate a risk-scoring system for predicting HIC in patients who underwent peroral endoscopic myotomy (POEM). METHODS: This study included patients with esophageal motility disorders who underwent POEM at our hospital between April 2015 and March 2023. HIC was defined as any of the following situations: fasting for gastrointestinal rest to manage adverse events (AEs); intravenous administration of medications such as antibiotics and blood transfusion; endoscopic, radiologic, and surgical interventions; intensive care unit management; or other life-threatening events. A risk-scoring system for predicting HIC after postoperative day (POD) 1 was developed using multivariable logistic regression and was internally validated using bootstrapping and decision curve analysis. RESULTS: Of the 589 patients, 50 (8.5%) experienced HIC after POD1. Risk scores were assigned for four factors as follows: age (0 points for <70 years, 1 point for 70-79 years, 2 points for ≥80 years), preoperative prognostic nutritional index (0 points for >45, 1 point for 40-45, 4 points for <40), postoperative surgical site AEs on second-look endoscopy (7 points), and postoperative pneumonia on chest radiography (6 points). The discriminative ability (concordance statistics, 0.85; 95% confidence interval, 0.78-0.91) and calibration (slope 1.00; 0.74-1.28) were satisfactory. The decision curve analysis demonstrated its clinical usefulness. CONCLUSION: This risk-scoring system can predict the HIC after POD1 and provide useful information for determining discharge.

The mntH gene of Burkholderia cenocepacia influences motility and quorum sensing to control virulence.

Quorum sensing (QS) signals widely exist in bacteria to control biological functions in response to populations of cells. Burkholderia cenocepacia, an important opportunistic pathogen in patients with cystic fibrosis (CF), is commonly found in the environment and mostly utilizes the N-acylhomoserine lactone (AHL) and cis-2-dodecenoic acid (BDSF) QS systems to control biological functions. Our previous study illuminated the detailed mechanism by which B.cenocepacia integrates BDSF and cyclic diguanosine monophosphate (c-di-GMP) signals to control virulence. Here, we employed Tn5 transposon mutagenesis to identify genes related to the BDSF QS system. One of the most significantly attenuated mutants had an insertion in the mntH gene. Here, we showed that MntH (Bcam0836), a manganese transport protein, controls QS-regulated phenotypes, including motility, biofilm formation and virulence. We also found that. BDSF production was attenuated at both the gene and signaling levels in the Bcam0836 mutant, and that Bcam0836 influenced the expression of some genes regulated by the BDSF receptor RpfR and the downstream regulator GtrR. These results show that the manganese transport protein. MntH modulates a subset of genes and functions regulated by the QS system in B. cenocepacia.

ERK1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motility.

ERK1/2 mitogen-activated protein kinases (ERK) are key regulators of basic cellular processes, including proliferation, survival, and migration. Upon phosphorylation, ERK becomes activated and a portion of it dimerizes. The importance of ERK activation in specific cellular events is generally well documented, but the role played by dimerization is largely unknown. Here, we demonstrate that impeding ERK dimerization precludes cellular movement by interfering with the molecular machinery that executes the rearrangements of the actin cytoskeleton. We also show that a constitutively dimeric ERK mutant can drive cell motility per se, demonstrating that ERK dimerization is both necessary and sufficient for inducing cellular migration. Importantly, we unveil that the scaffold protein kinase suppressor of Ras 1 (KSR1) is a critical element for endowing external agonists, acting through tyrosine kinase receptors, with the capacity to induce ERK dimerization and, subsequently, to unleash cellular motion. In agreement, clinical data disclose that high KSR1 expression levels correlate with greater metastatic potential and adverse evolution of mammary tumors. Overall, our results portray both ERK dimerization and KSR1 as essential factors for the regulation of cell motility and mammary tumor dissemination.

An unusual case of early onset opsoclonus-myoclonus syndrome: Case report and literature review.

Opsoclonus-myoclonus syndrome is a rare neurological condition characterized by opsoclonus, myoclonus, ataxia, irritability, and sleep disturbances. In pediatric patients, symptoms usually start between 16 and 18 months of age; opsoclonus-myoclonus syndrome presentation in children under 6 months is rare. Approximately 50% of cases are associated with neuroblastoma. We report an early onset presentation of opsoclonus-myoclonus syndrome in a previously healthy, 3-month-old female infant. The diagnostic workup revealed no abnormalities. The patient underwent monthly cycles of dexamethasone pulses and intravenous immunoglobulin with a favorable response. After a few months, the patient presented intermittent opsoclonus before the next scheduled pulse so from the 9th cycle onwards, the intravenous immunoglobulin dose was increased to 2 g/kg. After 9 months of treatment, she was diagnosed with a latent Mycobacterium tuberculosis infection. Due to this infection, dexamethasone pulses were discontinued, and intravenous immunoglobulin treatment was maintained with clinical improvement The patient received 18 intravenous immunoglobulin cycles, leaving her with a score of one on the Mitchell-Pike scale. Developmental milestones have been attained according to age. Despite the range of therapeutic options for managing opsoclonus-myoclonus syndrome described in the literature, the efficacy of these available therapies needs to be better established. A modified upfront approach with dexamethasone and intravenous immunoglobulin could be an option in settings where rituximab is unavailable.

Capacitation of ram spermatozoa promotes changes in energy metabolism and aquaporin 3 and is affected by individual testosterone variations.

BACKGROUND: Recently, the metabolic pathways involved in energy production and the role of aquaglyceroporins in capacitation-associated events have been studied in humans and mice. However, little is known about these in ram spermatozoa. OBJECTIVE: The present study investigated bioenergetic and aquaglyceroporin 3 variations during in vitro capacitation of ram spermatozoa. In addition, differences in testosterone levels between males were examined to determine their influence on capacitation-like changes. MATERIALS AND METHODS: Spermatozoa obtained from nine rams (ejaculates = 36) were incubated for 180 min in three different media (control, capacitating, and aquaglyceroporin-inhibitor media) at 38.5°C. At 0 and 180 min of incubation in each medium, sperm viability, kinetics, chlortetracycline patterns, adenosine triphosphate concentration, lactate excretion (final subproduct of glycolysis), and immunolocalization of aquaporin 3 were evaluated. RESULTS: The increment of the capacitated spermatozoa-chlortetracycline pattern and the hyperactivated-like movement characterized by the highest curvilinear velocity and amplitude of lateral head displacement and the lowest linearity was only recorded after 180 min in the capacitating medium. At this time and conditions, adenosine triphosphate content and lactate excretion decreased, whereas the aquaglyceroporin 3 location in the midpiece and principal piece increased compared to 0 min. Such changes were not observed in the control medium over time. Incubation in the aquaglyceroporin-inhibitor medium for 180 min reduced drastically sperm motility and adenosine triphosphate content compared to the other media. Testosterone analysis revealed a significant individual variability, which was also present in all sperm parameters evaluated. Furthermore, testosterone was negatively correlated with adenosine triphosphate content but positively correlated with lactate excretion levels, sperm viability, motility, capacitated sperm-chlortetracycline pattern, and aquaglyceroporin 3 immunolabeling in the midpiece and principal piece. CONCLUSION: Despite individual differences, capacitation of ram spermatozoa increases adenosine triphosphate consumption, energy metabolism, and aquaglyceroporin 3 location in the midpiece and principal piece, which seems to be related to the acquisition of hyperactivated-like motility. Furthermore, testosterone levels may serve as a valuable tool to select those males with a greater sperm metabolism rate and fertilizing capacity.

Flagellum-deficient Pseudomonas aeruginosa is more virulent than non-motile but flagellated mutants in a cystic fibrosis mouse model.

Loss of the flagellum marks the pathoadaptation of Pseudomonas aeruginosa to the cystic fibrosis (CF) airway environment during lung disease. Losing the flagellum is advantageous to the bacterium as the flagellum can be recognized by immune cells. The primary purpose of the flagellum is, however, to provide motility to the bacterium. Our goal was to determine whether the loss of flagellar motility or the loss of flagellum expression contributes to P. aeruginosa lung infection in CF. To address this, wild-type and gut-corrected FABP-human cystic fibrosis transmembrane conductance regulator (hCFTR) mice deficient in the murine Cftr gene were infected intratracheally with lethal doses of wild-type or flagellum-deficient P. aeruginosa. While there was no significant difference in the survival of wild-type mice after infection with either of the bacterial strains, a significantly higher mortality was observed in FABP-hCFTR mice infected with flagellum-deficient P. aeruginosa, compared to mice infected with their flagellated counterparts. When FABP-hCFTR mice were infected with isogenic, motility-deficient flagellated mutants, animal survival and lung bacterial titers were similar to those observed in mice infected with the wild-type bacterium. Airway levels of neutrophils and the amount neutrophil elastase were similar in mice infected with either the wild-type bacteria or the flagellum-deficient P. aeruginosa. Our results show that FABP-hCFTR mice have a different response to flagellum loss in P. aeruginosa compared to wild-type animals. The loss of flagellum expression, rather than the loss of motility, is the main driver behind the increased virulence of flagellum-deficient P. aeruginosa in CF. These observations provide new insight into P. aeruginosa virulence in CF.IMPORTANCEPseudomonas aeruginosa, a major respiratory pathogen in cystic fibrosis, is known to lose its flagellum during the course of infection in the airways. Here, we show that the loss of flagellum leads to a more enhanced virulence in Cftr-deficient cystic fibrosis mice than in control animals. Loss of flagellum expression, rather than the loss of flagellar swimming motility, represents the main driver behind this increased virulence suggesting that this appendage plays a specific role in P. aeruginosa virulence in cystic fibrosis airways.

[Thrombosis of the superior ophthalmic vein-A case series and review of the literature]. / Thrombose der Vena ophthalmica superior ­ Fallserie und Literaturübersicht.

BACKGROUND: Thrombosis of the superior ophthalmic vein (SOV) is rare. It can present with heterogeneous symptoms and requires a careful diagnostic work-up. METHODS: This article reports on a case series of three female patients with thrombosis of the SOV and performed an extensive review of the existing literature in PubMed. RESULTS: All three patients showed different leading symptoms but all had a triad of restricted eye motility, exophthalmos and a difference in intraocular pressure with the higher pressure on the side of the protruded eyeball. The pathophysiological background differed in all cases: in the two first cases a pre-existing anticoagulation treatment had been paused shortly before the event. Cofactors were an intraorbital venous outflow obstruction due to an unclear mass in the orbital apex in one case and hypercoagulability due to a malignant disease in the other case. In the third case, there was a cavernous sinus fistula. CONCLUSION: The diagnosis should be considered not only in patients with dilated vessels of the anterior segment but also in unclear cases of exophthalmos or unilateral elevated intraocular pressure (IOP).

VirB11, a traffic ATPase, mediated flagella assembly and type IV pilus morphogenesis to control the motility and virulence of Xanthomonas albilineans.

Xanthomonas albilineans (Xal) is a gram-negative bacterial pathogen responsible for developing sugarcane leaf scald disease, which engenders significant economic losses within the sugarcane industry. In the current study, homologous recombination exchange was carried out to induce mutations within the virB/D4-like type IV secretion system (T4SS) genes of Xal. The results revealed that the virB11-deletion mutant (ΔvirB11) exhibited a loss in swimming and twitching motility. Application of transmission electron microscopy analysis further demonstrated that the ΔvirB11 failed to develop flagella formation and type IV pilus morphology and exhibited reduced swarming behaviour and virulence. However, these alterations had no discernible impact on bacterial growth. Comparative transcriptome analysis between the wild-type Xal JG43 and the deletion-mutant ΔvirB11 revealed 123 differentially expressed genes (DEGs), of which 28 and 10 DEGs were notably associated with flagellar assembly and chemotaxis, respectively. In light of these findings, we postulate that virB11 plays an indispensable role in regulating the processes related to motility and chemotaxis in Xal.

Flagella and Cell Body Staining of Bacteria with Fluorescent Dyes.

Bacteria can propel themselves by rotating a flagellum or a flagellar bundle. To image this thin structure in motile bacteria, the flagella can be vitally stained with fluorophores. This chapter describes a flagellar staining protocol with the additional possibility of visualizing the cell body. It offers the opportunity to track conformational changes of flagella and simultaneously track the positions of the cell bodies. The additional use of a filter increases the number of motile cells and improves the signal-to-noise ratio of images. The flagellar staining requires a prior introduction of a surface-exposed cysteine, which is not covered in this chapter.

Discovery of oxazine-linked pyrimidine as an inhibitor of breast cancer growth and metastasis by abrogating NF-κB activation.

Introduction: Nuclear factor kappa (NF-κB) plays a key role in cancer cell proliferation; thus, small molecule inhibitors of NF-κB activity can effectively inhibit breast cancer (BC) progression. We have previously reported oxazine and piperazine-linked pyrimidines as novel anti-cancer agents that can suppress NF-κB activation in BC cells. Moreover, the TRX-01 compound, an oxazine-linked pyrimidine, inhibited MCF-7 cells at a concentration of 9.17 µM in the Alamar Blue assay. Methods: This work involved the analysis of frontier molecular orbitals, HOMO-LUMO interactions, and molecular electrostatic potential for the TRX-01 structure. Additionally, the TRX-01 compound was studied for cytotoxicity, and migration as well as invasion assays were performed on BC cells. Results: Finally, TRX-01 blocked the translocation of NF-κB from the cytoplasm to the nucleus in MCF-7 cells and reduced NF-κB and IκBα levels in a dose-dependent manner. It also suppressed migratory and invasive properties of BC cells. Conclusion: Overall, the data indicates that TRX-01 can function as a novel blocker of BC growth and metastasis by targeting NF-κB activation.

Prognostic factors for pediatric patients with severe intestinal motility disorders: a single institution's experience.

PURPOSE: To identify the prognostic factors for pediatric severe intestinal motility disorder (IMD). METHODS: We reviewed the medical records of patients with severe IMD, who required total parenteral nutrition (TPN) for ≥ 60 days at our institution between April, 1984 and March, 2023, examining their characteristics to identify prognostic factors. RESULTS: The types of IMD in the 14 patients enrolled in this study were as follows: isolated hypoganglionosis (IHG, n = 6), extensive aganglionosis (EAG: n = 6), and chronic idiopathic intestinal pseudo-obstruction (CIIP, n = 2). There was no significant difference in mortality among the three types of severe IMD. Weaning-off TPN and the use of the colon were not significant prognostic factors, but cholestasis was a significant prognostic factor (p = 0.005). There was a high mortality rate (50%), with the major causes of death being intestinal failure-associated liver disease (IFALD) following hepatic failure, and catheter-related blood stream infection (CRBSI). One IHG patient underwent small bowel transplantation but died of acute rejection. CONCLUSION: Severe IMD is still associated with a high mortality rate and cholestasis predicts the prognosis. Thus, preventing or improving IFALD and CRBSI caused by long-term TPN is important for reducing the mortality rate.

Perioperative Gastrointestinal Myoelectric Activity Measurement Using Wireless External Patches.

BACKGROUND: Stomach, small intestine, and colon have distinct patterns of contraction related to their function to mix and propel enteric contents. In this study, we aim to measure gut myoelectric activity in the perioperative course using external patches in an animal model. METHODS: Four external patches were placed on the abdominal skin of female Yucatan pigs to record gastrointestinal myoelectric signals for 3 to 5 d. Pigs subsequently underwent anesthesia and placement of internal electrodes on stomach, small intestine, and colon. Signals were collected by a wireless transmitter. Frequencies associated with peristalsis were analyzed for both systems for 6 d postoperatively. RESULTS: In awake pigs, we found frequency peaks in several ranges, from 4 to 6.5 cycles per minute (CPM), 8 to 11 CPM, and 14 to 18 CPM, which were comparable between subjects and concordant between internal and external recordings. The possible effect of anesthesia during the 1 or 2 h before surgical manipulation was observed as a 59% (±36%) decrease in overall myoelectric activity compared to the immediate time before anesthesia. The myoelectrical activity recovered quickly postoperatively. Comparing the absolute postsurgery activity levels to the baseline for each pig revealed higher overall activity after surgery by a factor of 1.69 ± 0.3. CONCLUSIONS: External patch measurements correlated with internal electrode recordings. Anesthesia and surgery impacted gastrointestinal myoelectric activity. Recordings demonstrated a rebound phenomenon in myoelectric activity in the postoperative period. The ability to monitor gastrointestinal tract myoelectric activity noninvasively over multiple days could be a useful tool in diagnosing gastrointestinal motility disorders.

Integrative Effects of Transcutaneous Electrical Acustimulation and Autonomic-Endocrine Mechanisms on Postprocedural Recovery in Patients With Endoscopic Retrograde Cholangio-Pancreatography.

OBJECTIVES: This study aimed to investigate the integrative effects and mechanisms of transcutaneous electrical acustimulation (TEA) on postprocedural recovery from endoscopic retrograde cholangio-pancreatography (ERCP). MATERIALS AND METHODS: A total of 86 patients for elective ERCP were randomly ordered to receive TEA (n = 43) at acupoints PC6 and ST36 or Sham-TEA (n = 43) at sham points from 24 hours before ERCP (pre-ERCP) to 24 hours after ERCP (PE24). Scores of gastrointestinal (GI) motility-related symptoms and abdominal pain, gastric slow waves, and autonomic functions were recorded through the spectral analysis of heart rate variability; meanwhile, circulatory levels of inflammation cytokines of tumor necrosis factor-α (TNF-α) and interleukin (IL)-10 and GI hormones of motilin, ghrelin, cholecystokinin (CCK), and vasoactive intestinal peptide (VIP) were assessed by enzyme-linked immunosorbent assay. RESULTS: 1) TEA, but not Sham-TEA, decreased the post-ERCP GI motility-related symptom score (2.4 ± 2.6 vs 7.9 ± 4.6, p < 0.001) and abdominal pain score (0.5 ± 0.7 vs 4.1 ± 2.7, p < 0.001) at PE24, and decreased the post-ERCP hospital day by 20.0% (p ＜0.05 vs Sham-TEA); 2) TEA improved the average gastric percentage of normal slow waves and dominant frequency by 34.6% and 33.3% at PE24, respectively (both p < 0.001 vs Sham-TEA); 3) TEA, but not Sham-TEA, reversed the ERCP-induced increase of TNF-α but not IL-10 at PE24, reflected as a significantly lower level of TNF-α in the TEA group than in the Sham-TEA group (1.6 ± 0.5 pg/mL vs 2.1 ± 0.9 pg/mL, p ＜ 0.01); 4) compared with Sham-TEA, TEA increased vagal activity by 37.5% (p ＜ 0.001); and 5) TEA caused a significantly higher plasma level of ghrelin (1.5 ± 0.8 ng/ml vs 1.1 ± 0.7 ng/ml, p ＜ 0.05) but not motilin, VIP, or CCK than did Sham-TEA at PE24. CONCLUSION: TEA at PC6 and ST36 accelerates the post-ERCP recovery, reflected as the improvement in GI motility and amelioration of abdominal pain, and suppression of the inflammatory cytokine TNF-α may mediate through both autonomic and ghrelin-related mechanisms.

The Motility of ß-Cyclodextrins Threaded on the Polyrotaxane Based Triblock Polymer and Its Influences on Mechanical Properties.

Polyrotaxane (PR) has garnered increasing attention due to its unique structure and exceptional performance. In this study, a polypseudorotaxane (PPR) initiator was prepared through the self-assembly of bromine-capped Pluronic F68 and ß-cyclodextrins (ß-CD) in water. Polyrotaxane-containing triblock copolymers (PR copolymers) were successfully synthesized by atom transfer radical polymerization (ATRP) of butyl methacrylate (BMA) using the PPR initiator in the presence of Cu(I)Br/PMDETA. The structure of the PR copolymers was thoroughly characterized using infrared spectroscopy (IR), proton nuclear magnetic resonance (1H NMR), and gel permeation chromatography (GPC). The mobility of ß-CD in the PR copolymers was demonstrated through dielectric measurements. Mechanical tests, including tensile strength assessments, thermal mechanical analysis, and dynamic mechanical analysis, confirmed the excellent mechanical properties and good processability of the PR copolymer, attributed to the PBMA blocks. Furthermore, the mechanical properties were found to be modulated by the motility of the threaded ß-CDs. Consequently, the superior mechanical properties and the high mobility of the threaded ß-CDs suggest promising potential for the as-prepared PR polymer in various advanced applications.

POEM for non-achalasia spastic oesophageal motility disorders.

Non-achalasia oesophageal motility disorders (NAOMD) represent a heterogeneous group of rare diseases, including oesophagogastric junction outflow obstruction, distal oesophageal spasm, and hypercontractile oesophagus. Despite the differing aetiological, manometric and pathophysiological characteristics, these disorders are unified by similar clinical presentation, including dysphagia and chest pain. The management of these disorders remain a challenge for the clinician. Pharmacotherapy, botulinum toxin injection, endoscopic dilation, and laparoscopic Heller myotomy have been employed, with limited efficacy in the majority of patients. Currently, there are no controlled studies in literature that suggest which is the best management of these diseases. Since its introduction in clinical practice, PerOral Endoscopic Myotomy (POEM) has emerged as a very promising, minimally invasive and effective treatment for oesophageal achalasia. No longer after the first uses, POEM has been successfully used also for the management of selected patients with NAOMD, However, currently available data are limited by small study sample sizes and short-term follow-up.

Feeding spent hemp biomass does not adversely affect fertility in rams.

OBJECTIVE: To determine the reproductive effects of feeding spent hemp biomass (SHB) to rams. Several studies suggest cannabidiols negatively affect reproductive characteristics, and the reproductive effects of SHB ingestion have not been investigated in any species. Spent hemp biomass is high in protein and essential fatty acids, indicating a potential use in livestock diets pending studies investigating its safety in animals. METHODS: Polypay rams approximately 6 months old were randomly assigned to 5 feeding trial groups (n = 7/group): either a low or high concentration of SHB in diet for either 4 or 8 weeks plus a control group. Blood samples were collected for hormone assays. At the conclusion of the feeding trial, the testes were removed, and sperm collected directly from the vas deferens were evaluated for motility (total, progressive, and speed), morphology, and concentration. A section from each ram's testes was formalin fixed, paraffin embedded, and subjected to routine immunohistochemistry to determine the expression of fertility-associated proteins deleted in azoospermia-like and Boule, followed by quantitative image analysis. RESULTS: Rams fed either 10% or 20% SHB for 8 weeks had significantly higher progressive sperm motility compared to controls. There were no significant differences between the treatment and control groups in the other parameters studied. Boule immunoexpression was adversely affected, whereas deleted in azoospermia-like immunoexpression was differentially affected by SHB ingestion. CONCLUSION: We conclude that up to 20% of the diet can be fed as SHB to rams for 8 weeks without adversely affecting testicular or sperm function. CLINICAL RELEVANCE: Supplementing young rams with SHB is unlikely to affect fertility.

Ninjinyoeito ameliorates anorexia and changes in peptide YY and ghrelin levels of cisplatin-treated mice.

We explored the effect of Ninjinyoeito (NYT) on cisplatin-induced anorexia, which reduces cancer patient survival. Both gastrointestinal motility and plasma concentrations of gastrointestinal peptides were assessed. Nine-week-old ICR female mice received intraperitoneal cisplatin injections (10 mg/kg) and daily oral NYT doses of 300 mg/kg (NYT300) or 1000 mg/kg (NYT1000). Plasma levels of gastrointestinal peptides were measured at 3 and 6 days after cisplatin injection. Gastrointestinal motility was assessed by analyzing the concentration of phenol red marker within sections of the gastrointestinal tract. Cisplatin-injected mice showed a decrease in daily food intake, but this effect was attenuated on day 5 with NYT1000 administration. Although plasma ghrelin levels were reduced on day 3 in cisplatin-treated mice, NYT1000 administration ameliorated this decrease. However, there were no differences in ghrelin levels among all groups on day 6. Levels of peptide YY (PYY) were elevated in the plasma of cisplatin-injected mice on days 3 and 6. Administration of NYT300 and NYT1000 suppressed the increase in PYY levels on day 6 but not on day 3. Gastrointestinal motility was impaired on day 6 in cisplatin-treated mice, but NYT1000 administration attenuated this effect. Our results suggest that NYT improves cisplatin-induced anorexia by suppressing alterations in ghrelin and PYY levels and by increasing gastrointestinal motility. Therefore, NYT may be a promising candidate for alleviating cisplatin-induced anorexia.

Pseudomonas aeruginosa surface motility and invasion into competing communities enhance interspecies antagonism.

Chronic polymicrobial infections involving Pseudomonas aeruginosa and Staphylococcus aureus are prevalent, difficult to eradicate, and associated with poor health outcomes. Therefore, understanding interactions between these pathogens is important to inform improved treatment development. We previously demonstrated that P. aeruginosa is attracted to S. aureus using type IV pili (TFP)-mediated chemotaxis, but the impact of attraction on S. aureus growth and physiology remained unknown. Using live single-cell confocal imaging to visualize microcolony structure, spatial organization, and survival of S. aureus during coculture, we found that interspecies chemotaxis provides P. aeruginosa a competitive advantage by promoting invasion into and disruption of S. aureus microcolonies. This behavior renders S. aureus susceptible to P. aeruginosa antimicrobials. Conversely, in the absence of TFP motility, P. aeruginosa cells exhibit reduced invasion of S. aureus colonies. Instead, P. aeruginosa builds a cellular barrier adjacent to S. aureus and secretes diffusible, bacteriostatic antimicrobials like 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO) into the S. aureus colonies. Reduced invasion leads to the formation of denser and thicker S. aureus colonies with increased HQNO-mediated lactic acid fermentation, a physiological change that could complicate treatment strategies. Finally, we show that P. aeruginosa motility modifications of spatial structure enhance competition against S. aureus. Overall, these studies expand our understanding of how P. aeruginosa TFP-mediated interspecies chemotaxis facilitates polymicrobial interactions, highlighting the importance of spatial positioning in mixed-species communities. IMPORTANCE: The polymicrobial nature of many chronic infections makes their eradication challenging. Particularly, coisolation of Pseudomonas aeruginosa and Staphylococcus aureus from airways of people with cystic fibrosis and chronic wound infections is common and associated with severe clinical outcomes. The complex interplay between these pathogens is not fully understood, highlighting the need for continued research to improve management of chronic infections. Our study unveils that P. aeruginosa is attracted to S. aureus, invades into neighboring colonies, and secretes anti-staphylococcal factors into the interior of the colony. Upon inhibition of P. aeruginosa motility and thus invasion, S. aureus colony architecture changes dramatically, whereby S. aureus is protected from P. aeruginosa antagonism and responds through physiological alterations that may further hamper treatment. These studies reinforce accumulating evidence that spatial structuring can dictate community resilience and reveal that motility and chemotaxis are critical drivers of interspecies competition.

Cotinine influences the effect of high and low nicotine concentrations on planarian motility differently.

Previous work from our laboratory showed that cotinine, a nicotine metabolite, reverses three nicotine-induced behavioral effects in freshwater planarians: motility decrease, seizure-like movements, and withdrawal-like behaviors. The present work explored whether cotinine, a nicotine metabolite, antagonized the nicotine-induced effects on planarian motility in a concentration-dependent manner. We found that nicotine decreased planarian motility at nicotine concentrations above 60 µM but increased planarian velocity at concentrations equal to or below 50 µM, in agreement with previous data. Cotinine did not affect planarian motility at a concentration range between 250 and 2750 µM. Furthermore, we found that cotinine alleviated the 100 µM nicotine-induced motility decrease in a concentration-dependent manner and reversed the low nicotine concentration motility increase, albeit in a concentration-independent manner. The apparent concentration-dependent alleviation of >60 µM nicotine-induced motility decrease by cotinine suggests an orthosteric relationship between nicotine and cotinine. On the other hand, the evident concentration-independent cotinine alleviation of the increase in motility induced by 50 µM nicotine suggests an allosteric relationship. Our data is consistent with the existing literature about the relationship between nicotine and cotinine in various models, reinforcing the case for the usefulness of the planarian model in pharmacological studies.

Effects of neuromuscular block reversal with neostigmine/glycopyrrolate versus sugammadex on bowel motility recovery after laparoscopic colorectal surgery: A randomized controlled trial.

STUDY OBJECTIVE: To compare the effects of neostigmine/glycopyrrolate (a traditional agent) and sugammadex on bowel motility recovery and the occurrence of digestive system complications after colorectal surgery. DESIGN: Prospective, randomized controlled trial. SETTING: A single tertiary center. PATIENTS: 111 patients undergoing laparoscopic colorectal surgery. INTERVENTIONS: Patients were randomized into two groups based on the block reversal agent: 1) a mixture of 50 µg.kg-1 of neostigmine and 10 µg.kg-1 of glycopyrrolate (neostigmine group) and 2) 2 mg.kg-1 of sugammadex (sugammadex group). MEASUREMENTS: The primary outcome was the time from the surgery's completion to the first flatus. The time to the first postoperative defecation, incidences of postoperative nausea or vomiting, ileus, and dry mouth, as well as postoperative length of stay, were also assessed. MAIN RESULTS: The time to the first flatus was significantly shorter in the sugammadex group than in the neostigmine group (59 [42-79] h vs 69 [53-90] h, P = 0.027). The time to the first defecation and the incidences of postoperative nausea or vomiting and ileus did not differ between the groups, nor did the postoperative length of stay. However, the incidence of postoperative dry mouth was significantly lower in the sugammadex group than in the neostigmine group (7 patients [13%] vs 39 patients [71%], P < 0.001). CONCLUSIONS: The time to the first flatus was shorter using 2 mg.kg-1 sugammadex to reverse the neuromuscular block for laparoscopic colorectal surgery compared to reversal with conventional neostigmine/glycopyrrolate.