Health-state utilities in long-term advanced melanoma survivors comparable with the general population.

BACKGROUND: Checkpoint inhibitors have been shown to substantially improve the survival of patients with advanced melanoma. With this growing group of survivors treated with immunotherapies, assessing their health-state utilities is essential and can be used for the calculation of quality-adjusted life years and for cost-effectiveness analyses. Therefore, we evaluated the health-state utilities in long-term advanced melanoma survivors. METHODS: Health-state utilities were evaluated in a cohort of advanced melanoma survivors 24-36 months (N = 37) and 36-plus months (N = 47) post-ipilimumab monotherapy. In addition, the health-state utilities of the 24-36 months survivor group were assessed longitudinally, and utilities of the combined survival groups (N = 84) were compared with a matched control population (N = 168). The EQ-5D was used to generate health-state utility values, and quality-of-life questionnaires were used to establish correlations and influencing factors of utility scores. RESULTS: Health-state utility scores were similar between the 24-36 months'- and the 36-plus months' survival group (0.81 vs 0.86; p = .22). In survivors, lower utility scores were associated with symptoms of depression (ß = - .82, p = .022) and fatigue burden (ß = - .29, p = .007). Utility scores did not significantly change after 24-36 months of survival, and the utilities of survivors were comparable to the matched control population (0.84 vs 0.87; p = .07). DISCUSSION: Our results show that long-term advanced melanoma survivors treated with ipilimumab monotherapy experience relatively stable and high health-state utility scores.

Health-related quality of life of long-term advanced melanoma survivors treated with anti-CTLA-4 immune checkpoint inhibition compared to matched controls.

BACKGROUND: Checkpoint inhibitors have changed overall survival for patients with advanced melanoma. However, there is a lack of data on health-related quality of life (HRQoL) of long-term advanced melanoma survivors, years after treatment. Therefore, we evaluated HRQoL in long-term advanced melanoma survivors and compared the study outcomes with matched controls without cancer. MATERIAL AND METHODS: Ipilimumab-treated advanced melanoma survivors without evidence of disease and without subsequent systemic therapy for a minimum of two years following last administration of ipilimumab were eligible for this study. The European Organization for Research and Treatment of Cancer quality of life questionnaire Core 30 (EORTC QLQ-C30), the Multidimensional Fatigue Inventory (MFI), the Hospital Anxiety and Depression Scale (HADS), and the Functional Assessment of Cancer Therapy-Melanoma questionnaire (FACT-M) were administered. Controls were individually matched for age, gender, and educational status. Outcomes of survivors and controls were compared using generalized estimating equations, and differences were interpreted as clinically relevant according to published guidelines. RESULTS: A total of 89 survivors and 265 controls were analyzed in this study. After a median follow-up of 39 (range, 17-121) months, survivors scored significantly lower on physical (83.7 vs. 89.8, difference (diff) = -5.80, p=.005), role (83.5 vs. 90, diff = -5.97, p=.02), cognitive (83.7 vs. 91.9, diff = -8.05, p=.001), and social functioning (86.5 vs. 95.1, diff = -8.49, p= <.001) and had a higher symptom burden of fatigue (23.0 vs. 15.5, diff = 7.48, p=.004), dyspnea (13.3 vs. 6.7, diff = 6.47 p=.02), diarrhea (7.9 vs. 4.0, diff = 3.78, p=.04), and financial impact (10.5 vs. 2.5, diff = 8.07, p=.001) than matched controls. Group differences were indicated as clinically relevant. DISCUSSION: Compared to matched controls, long-term advanced melanoma survivors had overall worse functioning scores, more physical symptoms, and financial difficulties. These data may contribute to the development of appropriate survivorship care.

Virology analyses of HCV genotype 4 isolates from patients treated with simeprevir and peginterferon/ribavirin in the Phase III RESTORE study.

Simeprevir is a hepatitis C virus NS3/4A protease inhibitor. Hepatitis C virus baseline NS3/4A polymorphisms and emerging mutations were characterized in treatment-naїve and treatment-experienced genotype 4-infected patients treated with simeprevir+peginterferon/ribavirin in the RESTORE study. Population sequencing of the NS3/4A region was performed and in vitro simeprevir activity against site-directed mutants or chimeric replicons with patient-derived NS3 protease sequences was assessed in a transient replicon assay. Simeprevir remained active against most (83/91 [91%]) baseline isolates tested in the chimeric replicon assay. Eight baseline isolates reduced simeprevir activity; these carried I132L or D168E substitutions reducing simeprevir median activity by 4.6- and 39-fold, respectively. Six of these eight isolates were from patients achieving sustained virologic response. Baseline NS3 Q80K polymorphism was not observed in the genotype 4-infected patients. Of the 107 simeprevir-treated patients, 37 did not achieve sustained virologic response for any reason. Of the 32 patients who failed treatment and had sequencing information, 28 (88%) had emerging mutations at NS3 positions 80, 122, 155, 156 and/or 168 at time of failure, similar to those in genotype 1. Emerging mutations were mainly D168V and D168E alone or combined with mutations at position 80. In general, isolates obtained at time of failure displayed high-level in vitro resistance to simeprevir (fold change ≥50) in a chimeric replicon assay with a median simeprevir fold change value of 440, consistent with observed mutations. In conclusion, emerging mutations in genotype 4 patients failing simeprevir+peginterferon/ribavirin treatment were similar to those in genotype 1 and conferred high-level resistance to simeprevir.

Activation of the PI3K/AKT pathway correlates with prognosis in stage II colon cancer.

BACKGROUND: Patients with UICC/AJCC stage II colon cancer have a high 5-year overall survival rate after surgery. Nevertheless, a significant subgroup of patients develops tumour recurrence. Currently, there are no clinically established biomarkers available to identify this patient group. We applied reverse-phase protein arrays (RPPA) for phosphatidylinositide-3-kinase pathway activation mapping to stratify patients according to their risk of tumour recurrence after surgery. METHODS: Full-length proteins were extracted from formalin-fixed, paraffin-embedded tissue samples of 118 patients who underwent curative resection. RPPA technology was used to analyse expression and/or phosphorylation levels of six major factors of the phosphatidylinositide-3-kinase pathway. Oncogenic mutations of KRAS and BRAF, and DNA microsatellite status, currently discussed as prognostic markers, were analysed in parallel. RESULTS: Expression of phospho-AKT (HR=3.52; P=0.032), S6RP (HR=6.3; P=0.044), and phospho-4E-BP1 (HR=4.12; P=0.011) were prognostic factors for disease-free survival. None of the molecular genetic alterations were significantly associated with prognosis. CONCLUSIONS: Our data indicate that activation of the PI3K/AKT pathway evidenced on the protein level might be a valuable prognostic marker to stratify patients for their risk of tumour recurrence. Beside adjuvant chemotherapy targeting of upregulated PI3K/AKT signalling may be an attractive strategy for treatment of high-risk patients.

A rapid ex vivo tissue model for optimising drug detection and ionisation in MALDI imaging studies.

The aim of this study was to establish an ex vivo model for a faster optimisation of sample preparation procedures, for example matrix choice, in matrix-assisted laser desorption/ionisation (MALDI) drug imaging studies. The ionisation properties of four drugs, afatinib, erlotinib, irinotecan and pirfenidone, were determined in an ex vivo tissue experiment by spotting decreasing dilution series onto liver sections. Hereby, the drug signals were distinctly detectable using different matrix compounds, which allowed the selection of the optimal matrix for each drug. The analysis of afatinib and erlotinib yielded high drug signals with α-cyano-4-hydroxycinnamic acid matrix, whereas 2,3-dihydroxybenzoic acid was identified as optimal matrix for irinotecan and pirfenidone detection. Our method was validated by a MALDI drug imaging approach of in vivo treated mouse tissue resulting in corresponding findings, indicating the spotting method as an appropriate approach to determine the matrix of choice. The present study shows the accordance between the detection of ex vivo spotted drugs and in vivo administered drugs by MALDI-TOF and MALDI-FT-ICR imaging, which has not been demonstrated so far. Our data suggest the ex vivo tissue spotting method as an easy and reliable model to optimise MALDI imaging measurements and to predict drug detection in tissue sections derived from treated mice prior to the recruitment of laboratory animals, which helps to save animals, time and costs.

Incidence of virological failure and emergence of resistance with twice-daily vs every 8-h administration of telaprevir in the OPTIMIZE study.

The OPTIMIZE study demonstrated noninferior efficacy between telaprevir (TVR) twice daily (bid) vs every 8-h (q8h) administration. This analysis compared the selective pressure of both dosing regimens by characterisation of the hepatitis C virus (HCV) variants emerging in genotype 1 (G1) HCV-infected patients who did not achieve sustained virological response (SVR). HCV NS3•4A population sequencing was performed at baseline and time of failure (viral breakthrough, stopping rule or relapse). TVR-resistant variants were classified by fold change in inhibitory concentration (IC50 ). Baseline TVR-resistance was low (<5%) and did not preclude achieving SVR in either arm. The proportion of patients with TVR-resistant variants at time of failure was similar in the bid (15%) and q8h (17%) dosing arms. The majority of variants and virological failures occurred in G1a patients, and mutations V36M, R155K and R155T (G1a), and V36A, T54A and A156S (G1b) were significantly enriched in both treatment arms. The number and type of emerging TVR-resistant variants in non-SVR patients were comparable between treatment arms and were consistent with previous observations. No differences in viral resistance profiles were observed between TVR-based treatment arms in non-SVR patients, indicating a similar selective pressure of TVR bid and q8h dosing.

Could hyponatremia be a marker of anastomotic leakage after colorectal surgery? A single center analysis of 1,106 patients over 5 years.

PURPOSE: The aim of this study is to define the significance of hyponatremia as a marker of anastomotic leakage after colorectal surgery. METHODS: All anastomoses in colorectal surgery performed at a single institution between July 2007 and July 2012 (n = 1,106) were retrospectively identified. Serum sodium levels and leukocyte values measured when an anastomotic leak was diagnosed by CT scan and/or surgical reintervention (n = 81) were compared to the values preferably on postoperative day 5 in the absence of an anastomotic leak (n = 1,025). RESULTS: The leak rate in anastomoses of the rectum was 9.0 %, while the leak rate of the other anastomoses was 5.4 %. Mean serum sodium level was 138.8 mmol/l in the group with an anastomotic leak and 140.5 mmol/l in the group without. Hyponatremia (<136 mmol/l) was present in 23 % of patients in the group with an anastomotic leak and in 15 % in the group without (p < 0.001). In multivariate analysis, leukocytes and serum sodium level remained as significant markers of an anastomotic leak. As a marker of an anastomotic leak, hyponatremia had a specificity of 93 % and a sensitivity of 23 %, while the presence of either leukocytosis or hyponatremia had a sensitivity of 68 %, a specificity of 75 %, a positive predictive value of 18 %, and a negative predictive value of 97 %. CONCLUSIONS: Hyponatremia could be a specific and relevant marker of anastomotic leakage after colorectal surgery. If hyponatremia and leukocytosis are present after colorectal surgery, anastomotic leakage should be suspected and a CT scan with rectal contrast dye is recommended.

[Terminology and manifestations of eruption disturbances]. / Terminologie en vormen van eruptiestoornissen.

Eruption disturbances of teeth are not unusual; many variations are encountered and eruption disturbances can negatively influence the development of the tooth and jaw system. Causes of eruption disturbances can be categorized into general and local factors. The clinical spectrum of eruption disturbances involves syndromic and non-syndromic problems for both kinds of factors, varying from delayed eruption to primary failure of eruption. The following types of eruption disturbances should be distinguished: impaction, primary retention, secondary retention and primary failure of eruption. Early detection of eruption disturbances and timely and appropriate treatment of the various eruption disturbances play an important role in preventing the negative effects of eruption disturbances on the development of the dentition and the craniofacial skeleton.

Specific activity of cyclin-dependent kinase I is a new potential predictor of tumour recurrence in stage II colon cancer.

BACKGROUND: There are no established biomarkers to identify tumour recurrence in stage II colon cancer. As shown previously, the enzymatic activity of the cyclin-dependent kinases 1 and 2 (CDK1 and CDK2) predicts outcome in breast cancer. Therefore, we investigated whether CDK activity identifies tumour recurrence in colon cancer. METHODS: In all, 254 patients with completely resected (R0) UICC stage II colon cancer were analysed retrospectively from two independent cohorts from Munich (Germany) and Leiden (Netherlands). None of the patients received adjuvant treatment. Development of distant metastasis was observed in 27 patients (median follow-up: 86 months). Protein expression and activity of CDKs were measured on fresh-frozen tumour samples. RESULTS: Specific activity (SA) of CDK1 (CDK1SA), but not CDK2, significantly predicted distant metastasis (concordance index=0.69, 95% confidence interval (CI): 0.55-0.79, P=0.036). Cutoff derivation by maximum log-rank statistics yielded a threshold of CDK1SA at 11 (SA units, P=0.029). Accordingly, 59% of patients were classified as high-risk (CDK1SA ≥11). Cox proportional hazard analysis revealed CDK1SA as independent prognostic variable (hazard ratio=6.2, 95% CI: 1.44-26.9, P=0.012). Moreover, CKD1SA was significantly elevated in microsatellite-stable tumours. CONCLUSION: Specific activity of CDK1 is a promising biomarker for metastasis risk in stage II colon cancer.

Enabling fiber optic serotyping of pathogenic bacteria through improved anti-fouling functional surfaces.

Significant research efforts are continually being directed towards the development of sensitive and accurate surface plasmon resonance biosensors for sequence specific DNA detection. These sensors hold great potential for applications in healthcare and diagnostics. However, the performance of these sensors in practical usage scenarios is often limited due to interference from the sample matrix. This work shows how the co-immobilization of glycol(PEG) diluents or 'back filling' of the DNA sensing layer can successfully address these problems. A novel SPR based melting assay is used for the analysis of a synthetic oligomer target as well as PCR amplified genomic DNA extracted from Legionella pneumophila. The benefits of sensing layer back filling on the assay performance are first demonstrated through melting analysis of the oligomer target and it is shown how back filling enables accurate discrimination of Legionella pneumophila serogroups directly from the PCR reaction product with complete suppression of sensor fouling.

High incidence and costs for anterior cruciate ligament reconstructions performed in Australia from 2003-2004 to 2007-2008: time for an anterior cruciate ligament register by Scandinavian model?

The aim of this paper was to provide a descriptive epidemiology of anterior cruciate ligament (ACL) reconstructions in Australia. Data on all ACL reconstructions were collected from July 1, 2003 till June 30, 2008. Main outcome measures were the incidence of ACL reconstructions for Australia, per age group, sex and sport, including estimates of direct costs. There were 50 187 ACL reconstructions over the 5-year period studied. The population-based incidence of ACL reconstructions per 100 000 person-years was 52.0 [95% confidence intervals (CI): 51.6; 52.5], higher than previously published incidences from other western countries (Scandinavia 32-38). The population incidence rose rapidly through adolescence and early adulthood and then gradually declined. Males had a higher population incidence than females. Skiing had the highest incidence of ACL reconstructions per 100 000 person-years, followed by Australian rules football, rugby, netball and soccer. The total estimated hospital costs associated with ACL reconstruction surgery were over A$75 million (€45 million) per year. Further research is necessary to examine the causes for the higher population incidence of ACL reconstructions in Australia compared with other countries. The establishment of a national register of ACL injuries, similar to those developed in Scandinavia should be considered.

Complex inheritance of larval adaptation in Plutella xylostella to a novel host plant.

Studying the genetics of host shifts and range expansions in phytophagous insects contributes to our understanding of the evolution of host plant adaptation. We investigated the recent host range expansion to pea, in the pea-adapted strain (P-strain) of the crucifer-specialist diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae). Larval survivorship on the novel host plant pea and a typical crucifer host (kale) was measured in reciprocal F(1), F(2) and backcrosses between the P-strain and a strain reared only on crucifers (C-strain). Reciprocal F(1) hybrids differed: offspring from P-strain mothers survived better on pea, indicating a maternal effect. However, no evidence for sex-linkage was found. Backcrosses to the P-strain produced higher survivorship on pea than C-strain backcrosses, suggesting recessive inheritance. In a linkage analysis with amplified fragment length polymorphism markers using P-strain backcrosses, two, four and five linkage groups contributing to survival on pea were identified in three different families respectively, indicating oligogenic inheritance. Thus, the newly evolved ability to survive on pea has a complex genetic basis, and the P-strain is still genetically heterogeneous and not yet fixed for all the alleles enabling it to survive on pea. Survivorship on kale was variable, but not related to survivorship on pea. This pattern may characterize the genetic inheritance of early host plant adaptation in oligophagous insect species.

Oviposition of diamondback moth in the presence and absence of a novel host plant.

The diamondback moth (DBM, Plutella xylostella L. (Lepidoptera: Plutellidae)) consumes a wide variety of brassicaceous host plants and is a common pest of crucifer crops worldwide. A highly unusual infestation of a sugar pea crop was recorded in Kenya in 1999, which persisted for two consecutive years. A strain (DBM-P) from this population was established in the laboratory and is the only one of several strains tested that can complete larval development on sugar peas. The oviposition acceptance and preference of the DBM-P strain was assessed in the presence of cabbage plants, sugar pea plants or both, in comparison to another strain (DBM-Cj) that was collected from cabbage and is unable to grow on pea plants. As expected, DBM-Cj females preferred to oviposit on cabbage plants. Surprisingly, DBM-P females also laid most eggs on cabbage and very few on peas. However, they laid significantly more eggs on the cabbage plant when pea plants were present. Our findings suggest that DBM-P manifested the initial stages of an evolutionary host range expansion, which is incomplete due to lack of oviposition fidelity on pea plants.

Chlamydia trachomatis intra-bacterial and total plasmid copy number in clinical urogenital samples.

Chlamydia trachomatis (CT) increases its plasmid numbers when stressed, as occurs in clinical trachoma samples. Most CT tests target the plasmid to increase the test sensitivity, but some only target the chromosome. We investigated clinical urogenital samples for total plasmid copy numbers to assess its diagnostic value and intra-bacterial plasmid copy numbers to assess its natural variation. Both plasmid and chromosome copies were quantified using qPCR, and the plasmid:chromosome ratio (PCr) calculated in two cohorts: (1) 383 urogenital samples for the total PCR (tPCr), and (2) 42 vaginal swabs, with one half treated with propium-monoazide (PMA) to prevent the quantification of extracellular DNA and the other half untreated to allow for both tPCr and intra-bacterial PCr (iPCr) quantification. Mann-Whitney U tests compared PCr between samples, in relation to age and gender. Cohort 1: tPCr varied greatly (1-677, median 16). Median tPCr was significantly higher in urines than vaginal swabs (32 vs. 11, p < 0.001). Cohort 2: iPCr was more stable than tPCr (range 0.1-3 vs. 1-11). To conclude, tPCr in urogenital samples was much more variable than previously described. Transport time and temperature influences DNA degradation, impacting chromosomal DNA more than plasmids and urine more than vaginal samples. Data supports a plasmid target in CT screening assays to increase clinical sensitivity.

Identification of a suppressor of the Dictyostelium profilin-minus phenotype as a CD36/LIMP-II homologue.

Profilin is an ubiquitous G-actin binding protein in eukaryotic cells. Lack of both profilin isoforms in Dictyostelium discoideum resulted in impaired cytokinesis and an arrest in development. A restriction enzyme-mediated integration approach was applied to profilin-minus cells to identify suppressor mutants for the developmental phenotype. A mutant with wild-type-like development and restored cytokinesis was isolated. The gene affected was found to code for an integral membrane glycoprotein of a predicted size of 88 kD containing two transmembrane domains, one at the NH2 terminus and the other at the COOH terminus. It is homologous to mammalian CD36/LIMP-II and represents the first member of this family in D. discoideum, therefore the name DdLIMP is proposed. Targeted disruption of the lmpA gene in the profilin-minus background also rescued the mutant phenotype. Immunofluorescence revealed a localization in vesicles and ringlike structures on the cell surface. Partially purified DdLIMP bound specifically to PIP2 in sedimentation and gel filtration assays. A direct interaction between DdLIMP and profilin could not be detected, and it is unclear how far upstream in a regulatory cascade DdLIMP might be positioned. However, the PIP2 binding of DdLIMP points towards a function via the phosphatidylinositol pathway, a major regulator of profilin.

Apoptin is modified by SUMO conjugation and targeted to promyelocytic leukemia protein nuclear bodies.

Apoptin, a protein of the chicken anemia virus (CAV), represents a novel potential anticancer therapeutic, because it induces apoptotic death specifically in tumor but not normal cells. The cellular localization appears to be crucial for apoptin's selective toxicity. In normal cells apoptin remains in the cytoplasm, whereas in transformed cells it migrates into the nucleus and kills the cell. However, the manner by which apoptin is able to distinguish between tumor and normal cells is unknown. Here, we report for the first time that apoptin interacts directly with the promyelocytic leukemia protein (PML) in tumor cells and accumulates in PML nuclear bodies (NBs), which are involved in apoptosis induction and viral replication. We also demonstrate that apoptin is sumoylated and that a sumoylation-deficient apoptin mutant is no longer recruited to PML-NBs, but localizes in the nuclear matrix. This mutant fails to bind PML, but can still induce apoptosis as efficiently as wild-type apoptin. Moreover, apoptin kills also PML-/- cells and promyelocytic leukemia cells with defective PML expression. Our results therefore suggest that apoptin kills tumor cells independently of PML and sumoylation, however, the interaction of apoptin with PML and small ubiquitin-like modifier (SUMO) proteins might be relevant for CAV replication.

Updating methods improved the performance of a clinical prediction model in new patients.

OBJECTIVE: Ideally, clinical prediction models are generalizable to other patient groups. Unfortunately, they perform regularly worse when validated in new patients and are then often redeveloped. While the original prediction model usually has been developed on a large data set, redevelopment then often occurs on the smaller validation set. Recently, methods to update existing prediction models with the data of new patients have been proposed. We used an existing model that preoperatively predicts the risk of severe postoperative pain (SPP) to compare five updating methods. STUDY DESIGN AND SETTING: The model was tested and updated with a set of 752 new patients (274 [36] with SPP). We studied the discrimination (ability to distinguish between patients with and without SPP) and calibration (agreement between the predicted risks and observed frequencies of SPP) of the five updated models in 283 other patients (100 [35%] with SPP). RESULTS: Simple recalibration methods improved the calibration to a similar extent as revision methods that made more extensive adjustments to the original model. Discrimination could not be improved by any of the methods. CONCLUSION: When the performance is poor in new patients, updating methods can be applied to adjust the model, rather than to develop a new model.

An introduction to optical super-resolution microscopy for the adventurous biologist.

Ever since the inception of light microscopy, the laws of physics have seemingly thwarted every attempt to visualize the processes of life at its most fundamental, sub-cellular, level. The diffraction limit has restricted our view to length scales well above 250 nm and in doing so, severely compromised our ability to gain true insights into many biological systems. Fortunately, continuous advancements in optics, electronics and mathematics have since provided the means to once again make physics work to our advantage. Even though some of the fundamental concepts enabling super-resolution light microscopy have been known for quite some time, practically feasible implementations have long remained elusive. It should therefore not come as a surprise that the 2014 Nobel Prize in Chemistry was awarded to the scientists who, each in their own way, contributed to transforming super-resolution microscopy from a technological tour de force to a staple of the biologist's toolkit. By overcoming the diffraction barrier, light microscopy could once again be established as an indispensable tool in an age where the importance of understanding life at the molecular level cannot be overstated. This review strives to provide the aspiring life science researcher with an introduction to optical microscopy, starting from the fundamental concepts governing compound and fluorescent confocal microscopy to the current state-of-the-art of super-resolution microscopy techniques and their applications.

Inactivation of lmpA, encoding a LIMPII-related endosomal protein, suppresses the internalization and endosomal trafficking defects in profilin-null mutants.

Profilin is a key phosphoinositide and actin-binding protein connecting and coordinating changes in signal transduction pathways with alterations in the actin cytoskeleton. Using biochemical assays and microscopic approaches, we demonstrate that profilin-null cells are defective in macropinocytosis, fluid phase efflux, and secretion of lysosomal enzymes but are unexpectedly more efficient in phagocytosis than wild-type cells. Disruption of the lmpA gene encoding a protein (DdLIMP) belonging to the CD36/LIMPII family suppressed, to different degrees, most of the profilin-minus defects, including the increase in F-actin, but did not rescue the secretion defect. Immunofluorescence microscopy indicated that DdLIMP, which is also capable of binding phosphoinositides, was associated with macropinosomes but was not detected in the plasma membrane. Also, inactivation of the lmpA gene in wild-type strains resulted in defects in macropinocytosis and fluid phase efflux but not in phagocytosis. These results suggest an important role for profilin in regulating the internalization of fluid and particles and the movement of material along the endosomal pathway; they also demonstrate a functional interaction between profilin and DdLIMP that may connect phosphoinositide-based signaling through the actin cytoskeleton with endolysosomal membrane trafficking events.