Comparative biomechanics of hagfish skins: diversity in material, morphology, and movement.

The baggy skins of hagfishes confer whole-body flexibility that enables these animals to tie themselves into knots without injury. The skin's looseness is produced by a subcutaneous blood sinus that decouples the skin and body core and permits the core to contort dramatically without loading the skin in tension or shear. Hagfish skin represents a biological composite material comparable in strength and stiffness to the conventionally taut skins of other fishes. However, our understanding of hagfish skin is restricted to only one of 78 species: The Pacific hagfish Eptatretus stoutii. To determine if other hagfish share similar characteristics with E. stoutii, we measured material properties and compared histological data sets from the skins of four hagfish species: E. springeri, E. stoutii, Myxine glutinosa, and M. hubbsi. We also compared these material properties data with skins from the American eel, Anguilla rostrata. We subjected skin samples from all species to uniaxial tensile tests in order to measure strength, stiffness, extensibility, and toughness of skins stretched along longitudinal and circumferential axes. We also used a series of equibiaxial tensile tests on skin samples from E. stoutii, M. glutinosa, and A. rostrata to measure stiffness of skins simultaneously strained along both axes. Significant results of uniaxial and biaxial tests show that the skins from Eptatretus are anisotropic, being stiffer in the longitudinal axis, and more extensible than the isotropic skins of Myxine. Skins of A. rostrata were stiffer in the circumferential axis and they were stronger, tougher, and stiffer than all hagfish skins examined. The skins of Eptatretus are histologically distinct from Myxine skins and possess arrays of fibers that stain like muscle. These interspecific differences across hagfish skins show a phylogenetic pattern with knotting kinematics and flexibility; both genera belong to distinct but major subfamilies within the Myxinidae, and Eptatretus is known for creating and manipulating a greater diversity of knotting styles than Myxine.

Ocular Tolerance of Contemporary Electronic Display Devices.

Electronic displays have become an integral part of life in the developed world since the revolution of mobile computing a decade ago. With the release of multiple consumer-grade virtual reality (VR) and augmented reality (AR) products in the past 2 years utilizing head-mounted displays (HMDs), as well as the development of low-cost, smartphone-based HMDs, the ability to intimately interact with electronic screens is greater than ever. VR/AR HMDs also place the display at much closer ocular proximity than traditional electronic devices while also isolating the user from the ambient environment to create a "closed" system between the user's eyes and the display. Whether the increased interaction with these devices places the user's retina at higher risk of damage is currently unclear. Herein, the authors review the discovery of photochemical damage of the retina from visible light as well as summarize relevant clinical and preclinical data regarding the influence of modern display devices on retinal health. Multiple preclinical studies have been performed with modern light-emitting diode technology demonstrating damage to the retina at modest exposure levels, particularly from blue-light wavelengths. Unfortunately, high-quality in-human studies are lacking, and the small clinical investigations performed to date have failed to keep pace with the rapid evolutions in display technology. Clinical investigations assessing the effect of HMDs on human retinal function are also yet to be performed. From the available data, modern consumer electronic displays do not appear to pose any acute risk to vision with average use; however, future studies with well-defined clinical outcomes and illuminance metrics are needed to better understand the long-term risks of cumulative exposure to electronic displays in general and with "closed" VR/AR HMDs in particular. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:346-354.].

Nonnative Gracilaria vermiculophylla tetrasporophytes are more difficult to debranch and are less nutritious than gametophytes.

Theory predicts that the maintenance of haplodiplontic life cycles requires ecological differences between the haploid gametophytes and diploid sporophytes, yet evidence of such differences remain scarce. The haplodiplontic red seaweed Gracilaria vermiculophylla has invaded the temperate estuaries of the Northern Hemisphere, where it commonly modifies detrital and trophic pathways. In native populations, abundant hard substratum enables spore settlement, and gametophyte:tetrasporophyte ratios are ~40:60. In contrast, many non-native populations persist in soft-sediment habitats without abundant hard substratum, and can be 90%-100% tetrasporophytic. To test for ecologically relevant phenotypic differences, we measured thallus morphology, protein content, organic content, "debranching resistance" (i.e., tensile force required to remove a branch from its main axis node), and material properties between male gametophytes, female gametophytes, and tetrasporophytes from a single, nonnative site in Charleston Harbor, South Carolina, USA in 2015 and 2016. Thallus length and surface area to volume ratio differed between years, but were not significantly different between ploidies. Tetrasporophytes had lower protein content than gametophytes, suggesting the latter may be more attractive to consumers. More force was required to pull a branch from the main axis of tetrasporophytes relative to gametophytes. A difference in debranching resistance may help to maintain tetrasporophyte thallus durability relative to gametophytes, providing a potential advantage in free-floating populations. These data may shed light on the invasion ecology of an important ecosystem engineer, and may advance our understanding of life cycle evolution and the maintenance of life cycle diversity.

Synthetic Study toward Total Synthesis of (±)-Germine: Synthesis of (±)-4-Methylenegermine.

The total synthesis of 4-methylenegermine is described.

Direct valorisation of waste cocoa butter triglycerides via catalytic epoxidation, ring-opening and polymerisation.

BACKGROUND: Development of circular economy requires significant advances in the technologies for valorisation of waste, as waste becomes new feedstock. Food waste is a particularly important feedstock, containing large variation of complex chemical functionality. Although most food waste sources are complex mixtures, waste from food processing, no longer suitable for the human food chain, may also represent relatively clean materials. One such material requiring valorisation is cocoa butter. RESULTS: Epoxidation of a triglyceride from a food waste source, processing waste cocoa butter, into the corresponding triglyceride epoxide was carried out using a modified Ishii-Venturello catalyst in batch and continuous flow reactors. The batch reactor achieved higher yields due to the significant decomposition of hydrogen peroxide in the laminar flow tubular reactor. Integral and differential models describing the reaction and the phase transfer kinetics were developed for the epoxidation of cocoa butter and the model parameters were estimated. Ring-opening of the epoxidised cocoa butter was undertaken to provide polyols of varying molecular weight (Mw = 2000-84 000 Da), hydroxyl value (27-60 mg KOH g-1) and acid value (1-173 mg KOH g-1), using either aqueous ortho-phosphoric acid (H 3 PO 4) or boron trifluoride diethyl etherate (BF 3·OEt2)-mediated oligomerisation in bulk, using hexane or tetrahydrofuran (THF) as solvents. The thermal and tensile properties of the polyurethanes obtained from the reaction of these polyols with 4,4'-methylene diphenyl diisocyanate (MDI) are described. CONCLUSION: The paper presents a complete valorisation scheme for a food manufacturing industry waste stream, starting from the initial chemical transformation, developing a process model for the design of a scaled-up process, and leading to synthesis of the final product, in this case a polymer. This work describes aspects of optimisation of the conversion route, focusing on clean synthesis and also demonstrates the interdisciplinary nature of the development projects, requiring input from different areas of chemistry, process modelling and process design. © 2017 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

A chemical genomics approach to drug reprofiling in oncology: Antipsychotic drug risperidone as a potential adenocarcinoma treatment.

Drug reprofiling is emerging as an effective paradigm for discovery of cancer treatments. Herein, an antipsychotic drug is immobilised using the Magic Tag® chemical genomics tool and screened against a T7 bacteriophage displayed library of polypeptides from Drosophila melanogaster, as a whole genome model, to uncover an interaction with a section of 17-ß-HSD10, a proposed prostate cancer target. A computational study and enzyme inhibition assay with full length human 17-ß-HSD10 identifies risperidone as a drug reprofiling candidate. When formulated with rumenic acid, risperidone slows proliferation of PC3 prostate cancer cells in vitro and retards PC3 prostate cancer tumour growth in vivo in xenografts in mice, presenting an opportunity to reprofile risperidone as a cancer treatment.

Pilot trial of CRLX101 in patients with advanced, chemotherapy-refractory gastroesophageal cancer.

BACKGROUND: CRLX101 is an investigational nanoparticle-drug conjugate with a camptothecin payload. Preclinical evidence indicated preferential uptake in tumors, and tumor xenograft models demonstrate superiority of CRLX101 over irinotecan. A pilot trial was conducted at recommended phase 2 dosing (RP2D) using the bimonthly schedule to assess preferential uptake of CRLX101 in tumor vs. adjacent normal tissue in endoscopically accessible tumors in chemotherapy-refractory gastroesophageal cancer. Results from the biopsies were previously reported and herein we present the clinical outcomes. METHODS: Patients initiated CRLX101 dosed at RP2D (15 mg/m2) on days 1 and 15 of a 28-day cycle. Detection of preferential CRLX101 tumor uptake was the primary endpoint and objective response rate (ORR) was a secondary endpoint. With a sample size of ten patients, the study had 90% power to detect ≥1 responder if the true response rate is ≥21%. RESULTS: Between Dec. 2012 and Dec. 2014, ten patients with chemotherapy-refractory (median 2 prior lines of therapy, range 1-4) gastric adenocarcinoma were enrolled. The median time-to-progression was 1.7 months. Best response was seen in one patient with stable disease (SD) for 8 cycles. Only ≥ grade 3 drug-related toxicity occurred in one patient with grade 3 cardiac chest pain who was able to resume therapy after CRLX101 was reduced to 12 mg/m2. CONCLUSIONS: Bimonthly CRLX101 demonstrated minimal activity with SD as best response in this heavily pretreated population. Future efforts with CRLX101 in gastric cancer should focus on combination and more dose-intensive strategies given its favorable toxicity profile and evidence of preferential tumor uptake.

Material Properties of Hagfish Skin, with Insights into Knotting Behaviors.

Hagfishes (Myxinidae) often integrate whole-body knotting movements with jawless biting motions when reducing large marine carcasses to ingestible items. Adaptations for these behaviors include complex arrangements of axial muscles and flexible, elongate bodies without vertebrae. Between the axial muscles and the hagfish skin is a large, blood-filled subcutaneous sinus devoid of the intricate, myoseptal tendon networks characteristic of the taut skins of other fishes. We propose that the loose-fitting skin of the hagfish facilitates the formation and manipulation of body knots, even if it is of little functional significance to steady swimming. Hagfish skin is a relatively thick, anisotropic, multilayered composite material comprising a superficial, thin, and slimy epidermis, a middle dermal layer densely packed with fibrous tissues, and a deep subdermal layer comprised of adipose tissue. Hagfish skin is stiffer when pulled longitudinally than circumferentially. Stress-strain data from uniaxial tensile tests show that hagfish skins are comparable in tensile strength and stiffness to the taut skins of elongate fishes that do not engage in knotting behaviors (e.g., sea lamprey and penpoint gunnel). Sheath-core-constructed ropes, which serve as more accurate models for hagfish bodies, demonstrate that loose skin (extra sheathing) enhances flexibility of the body (rope). Along with a loose-fitting skin, the morphologies of hagfish skin parallel those of moray eels, which are also known for generating and manipulating figure-eight-style body knots when struggling with prey.

Axially Chiral Enamides: Substituent Effects, Rotation Barriers, and Implications for their Cyclization Reactions.

The barrier to rotation around the N-alkenyl bond of 38 N-alkenyl-N-alkylacetamide derivatives was measured (ΔG(⧧) rotation varied between <8.0 and 31.0 kcal mol(-1)). The most important factor in controlling the rate of rotation was the level of alkene substitution, followed by the size of the nitrogen substituent and, finally, the size of the acyl substituent. Tertiary enamides with four alkenyl substituents exhibited half-lives for rotation between 5.5 days and 99 years at 298 K, sufficient to isolate enantiomerically enriched atropisomers. The radical cyclizations of a subset of N-alkenyl-N-benzyl-α-haloacetamides exhibiting relatively high barriers to rotation round the N-alkenyl bond (ΔG(⧧) rotation >20 kcal mol(-1)) were studied to determine the regiochemistry of cyclization. Those with high barriers (>27 kcal mol(-1)) did not lead to cyclization, but those with lower values produced highly functionalized γ-lactams via a 5-endo-trig radical-polar crossover process that was terminated by reduction, an unusual cyclopropanation sequence, or trapping with H2O, depending upon the reaction conditions. Because elevated temperatures were necessary for cyclization, this precluded study of the asymmetric transfer in the reaction of individual atropisomers. However, enantiomerically enriched atropsiomeric enamides should be regarded as potential asymmetric building blocks for reactions that can be accomplished at room temperature.

CRLX101 nanoparticles localize in human tumors and not in adjacent, nonneoplastic tissue after intravenous dosing.

Nanoparticle-based therapeutics are being used to treat patients with solid tumors. Whereas nanoparticles have been shown to preferentially accumulate in solid tumors of animal models, there is little evidence to prove that intact nanoparticles localize to solid tumors of humans when systemically administered. Here, tumor and adjacent, nonneoplastic tissue biopsies are obtained through endoscopic capture from patients with gastric, gastroesophageal, or esophageal cancer who are administered the nanoparticle CRLX101. Both the pre- and postdosing tissue samples adjacent to tumors show no definitive evidence of either the nanoparticle or its drug payload (camptothecin, CPT) contained within the nanoparticle. Similar results are obtained from the predosing tumor samples. However, in nine of nine patients that were evaluated, CPT is detected in the tumor tissue collected 24-48 h after CRLX101 administration. For five of these patients, evidence of the intact deposition of CRLX101 nanoparticles in the tumor tissue is obtained. Indications of CPT pharmacodynamics from tumor biomarkers such as carbonic anhydrase IX and topoisomerase I by immunohistochemistry show clear evidence of biological activity from the delivered CPT in the posttreatment tumors.

Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core.

Most therapeutic agents are excluded from entering the central nervous system by the blood-brain barrier (BBB). Receptor mediated transcytosis (RMT) is a common mechanism used by proteins, including transferrin (Tf), to traverse the BBB. Here, we prepared Tf-containing, 80-nm gold nanoparticles with an acid-cleavable linkage between the Tf and the nanoparticle core to facilitate nanoparticle RMT across the BBB. These nanoparticles are designed to bind to Tf receptors (TfRs) with high avidity on the blood side of the BBB, but separate from their multidentate Tf-TfR interactions upon acidification during the transcytosis process to allow release of the nanoparticle into the brain. These targeted nanoparticles show increased ability to cross an in vitro model of the BBB and, most important, enter the brain parenchyma of mice in greater amounts in vivo after systemic administration compared with similar high-avidity nanoparticles containing noncleavable Tf. In addition, we investigated this design with nanoparticles containing high-affinity antibodies (Abs) to TfR. With the Abs, the addition of the acid-cleavable linkage provided no improvement to in vivo brain uptake for Ab-containing nanoparticles, and overall brain uptake was decreased for all Ab-containing nanoparticles compared with Tf-containing ones. These results are consistent with recent reports of high-affinity anti-TfR Abs trafficking to the lysosome within BBB endothelium. In contrast, high-avidity, Tf-containing nanoparticles with the acid-cleavable linkage avoid major endothelium retention by shedding surface Tf during their transcytosis.

Mechanical properties of the cuticles of three cockroach species that differ in their wind-evoked escape behavior.

The structural and material properties of insect cuticle remain largely unexplored, even though they comprise the majority (approximately 80%) of animals. Insect cuticle serves many functions, including protection against predatory attacks, which is especially beneficial to species failing to employ effective running escape responses. Despite recent advances in our understanding of insect escape behaviors and the biomechanics of insect cuticle, there are limited studies on the protective qualities of cuticle to extreme mechanical stresses and strains imposed by predatory attacks, and how these qualities vary between species employing different escape responses. Blattarians (cockroaches) provide an appropriate model system for such studies. Wind-evoked running escape responses are strong in Periplaneta americana, weak in Blaberus craniifer and absent in Gromphodorhina portentosa, putting the latter two species at greater risk of being struck by a predator. We hypothesized that the exoskeletons in these two larger species could provide more protection from predatory strikes relative to the exoskeleton of P. americana. We quantified the protective qualities of the exoskeletons by measuring the puncture resistance, tensile strength, strain energy storage, and peak strain in fresh samples of thoracic and abdominal cuticles from these three species. We found a continuum in puncture resistance, tensile strength, and strain energy storage between the three species, which were greatest in G. portentosa, moderate in B. craniifer, and smallest in P. americana. Histological measurements of total cuticle thickness followed this same pattern. However, peak strain followed a different trend between species. The comparisons in the material properties drawn between the cuticles of G. portentosa, B. craniifer, and P. americana demonstrate parallels between cuticular biomechanics and predator running escape responses.

A chemical genomics approach to identification of interactions between bioactive molecules and alternative reading frame proteins.

Magic Tag® immobilisation of bioactive molecules coupled with bacteriophage display, followed by an ELISA assay, provides a protocol that can probe interactions of drugs with putative products of alternative initiation of translation as exemplified by the binding of immobilised flecainide to protein products of genes linked to sudden cardiac death.

Atom-transfer cyclization with CuSO4/KBH4: a formal "activators generated by electron transfer" process also applicable to atom-transfer polymerization.

The 4-exo and 5-exo-trig atom-transfer cyclizations of 1, 8a-e, 9, 12, and 13 can be mediated with as little as 0.05 mol % of Cu(TPMA)SO(4)·5H(2)O in the presence of 2.5 mol % of borohydride salts in 10 min at room temperature in air. This formal "activators generated by electron transfer" (AGET) procedure utilizes a cheap and oxidatively stable copper source (CuSO(4)·5H(2)O) and can be carried out in environmentally benign solvents (EtOH). It is possible to alter the product distribution in the 5-endo radical-polar crossover reactions of 10a,b and 11 by tailoring the amount of borohydride. Cyclization onto alkynes 14 and 15 is also possible in only 20 min. Controlled radical polymerization of styrene, with increased rates over conventional atom-transfer radical polymerization (ATRP), can be carried out in a controlled fashion (Mn, PDI) using either CuBr or CuSO(4)·5H(2)O and Bu(4)NBH(4).

A spectrometer designed for 6.7 and 14.1 T DNP-enhanced solid-state MAS NMR using quasi-optical microwave transmission.

A Dynamic Nuclear Polarisation (DNP) enhanced solid-state Magic Angle Spinning (MAS) NMR spectrometer operating at 6.7 T is described and demonstrated. The 187 GHz TE(13) fundamental mode of the FU CW VII gyrotron is used as the microwave source for this magnetic field strength and 284 MHz (1)H DNP-NMR. The spectrometer is designed for use with microwave frequencies up to 395 GHz (the TE(16) second-harmonic mode of the gyrotron) for DNP at 14.1T (600 MHz (1)H NMR). The pulsed microwave output from the gyrotron is converted to a quasi-optical Gaussian beam using a Vlasov antenna and transmitted to the NMR probe via an optical bench, with beam splitters for monitoring and adjusting the microwave power, a ferrite rotator to isolate the gyrotron from the reflected power and a Martin-Puplett interferometer for adjusting the polarisation. The Gaussian beam is reflected by curved mirrors inside the DNP-MAS-NMR probe to be incident at the sample along the MAS rotation axis. The beam is focussed to a ~1 mm waist at the top of the rotor and then gradually diverges to give much more efficient coupling throughout the sample than designs using direct waveguide irradiation. The probe can be used in triple channel HXY mode for 600 MHz (1)H and double channel HX mode for 284 MHz (1)H, with MAS sample temperatures ≥85 K. Initial data at 6.7 T and ~1 W pulsed microwave power are presented with (13)C enhancements of 60 for a frozen urea solution ((1)H-(13)C CP), 16 for bacteriorhodopsin in purple membrane ((1)H-(13)C CP) and 22 for (15)N in a frozen glycine solution ((1)H-(15)N CP) being obtained. In comparison with designs which irradiate perpendicular to the rotation axis the approach used here provides a highly efficient use of the incident microwave beam and an NMR-optimised coil design.

Bond rotation dynamics of enamides: the effect of the acyl group and potential for chirality transfer during 5-endo trig radical cyclizations.

Barriers to rotation of the N-alkenyl bond in a series of N-cycloalkenyl-N-benzyl acetamide derivatives have been measured in different solvents by variable-temperature NMR experiments. The barriers range from 9.7 to 14.2 kcal/mol, depending on substituents on the acetamide acyl group. Polar solvents such as chloroform and methanol increase the barrier to rotation compared to nonpolar solvents such as toluene. The barrier to rotation of "mimics" for acetamide-based radicals are estimated. The relative order of the values of k(rot) for different acyl groups parallels their reported Taft E(s) paramaters. For successful chirality transfer in 5-endo trig radical cyclization, it is evident that rotations would need to be significantly slower than those reported here.

Posture, speed, and habitat structure: three-dimensional hindlimb kinematics of two species of padless geckos.

Differences in habitat use are often correlated with differences in morphology and behavior, while animals in similar habitats often exhibit similarities in form and function. However, this has not been tested extensively among lizards, especially geckos. Most studies of gecko locomotion have focused on the ability to adhere to surfaces. However, there are several species of geckos that have either secondarily lost adhesive capabilities or simply lack the capability. We quantified the three-dimensional locomotor kinematics for two desert-dwelling padless geckos, Teratoscincus scincus and Eublepharis macularius, on a level trackway over a range of speeds. Our results indicate that T. scincus landed with a high relative hip height of 48.7 ± 2.4% of total limb length at footfall, while E. macularius exhibited hip heights averaging only 36.0 ± 1.8% of total limb length for footfall. The three-dimensional knee angle of T. scincus averaged 120.6 ± 3.9° at footfall, while E. macularius averaged only 101.6 ± 1.8° at footfall. In addition, the femur of E. macularius was elevated to a much greater extent (i.e., was closer to being perpendicular to the long axis of the body) than that of T. scincus and every other lizard that has been studied, suggesting they move with a "hyper-sprawled" posture. Both of these gecko species live in deserts, but T. scincus is psammophilic while E. macularius inhabits a rocky, more densely vegetated environment. Benefits of the more upright posture of T. scincus on open sandy habitat may include a greater field of view and more efficient locomotion. The more sprawled posture of E. macularius may lower its center of gravity and aid in balance while climbing on rocks or shrubs.

Slipping, sliding and stability: locomotor strategies for overcoming low-friction surfaces.

Legged terrestrial animals must avoid falling while negotiating unexpected perturbations inherent to their structurally complex environments. Among humans, fatal and nonfatal injuries frequently result from slip-induced falls precipitated by sudden unexpected encounters with low-friction surfaces. Although studies using walking human models have identified some causes of falls and mechanisms underlying slip prevention, it is unclear whether these apply to various locomotor speeds and other species. We used high-speed video and inverse dynamics to investigate the locomotor biomechanics of helmeted guinea fowl traversing slippery surfaces at variable running speeds (1.3-3.6 m s(-1)). Falls were circumvented when limb contact angles exceeded 70 deg, though lower angles were tolerated at faster running speeds (>3.0 m s(-1)). These prerequisites permitted a forward shift of the body's center of mass over the limb's base of support, which kept slip distances below 10 cm (the threshold distance for falls) and maximized the vertical ground reaction forces, thus facilitating limb retraction and the conclusion of the stance phase. These postural control strategies for slip avoidance parallel those in humans, demonstrating the applicability of these strategies across locomotor gaits and the potential for guinea fowl as an insightful model for invasive approaches to understanding limb neuromuscular control on slippery surfaces.

Degradation product emission from historic and modern books by headspace SPME/GC-MS: evaluation of lipid oxidation and cellulose hydrolysis.

Volatile organic compounds emitted from a several decade series of bound periodicals (1859-1939) printed on ground wood paper, as well as historical books dating from the 1500s to early 1800s made from cotton/linen rag, were studied using an improved headspace SPME/GC-MS method. The headspace over the naturally aging books, stored upright in glass chambers, was monitored over a 24-h period, enabling the identification of a wide range of organic compounds emanating from the whole of the book. The detection of particular straight chain aldehydes, as well as characteristic alcohols, alkenes and ketones is correlated with oxidative degradation of the C(18) fatty acid constituency of paper. The relative importance of hydrolytic and oxidative chemistry involved in paper aging in books published between 1560 and 1939 was examined by comparing the relative abundances of furfural (FUR) a known cellulose hydrolysis product, and straight chain aldehydes (SCA) produced from the oxidation of fatty acids in paper. The relative abundance of furfural is shown to increase across the 379-year publication time span. A comparison of relative SCA peak areas across the series of books examined reveals that SCA emission is more important in the cotton/linen rag books than in the ground wood books.

Prolonged use of thromboprophylaxis may not be necessary in laparoscopic colorectal surgery.

PURPOSE: Patients undergoing colorectal resections are considered high risk for developing thromboembolic disease. We postulate, however, that the rapid recovery and swift mobilization after laparoscopic resections reduce this risk and that these patients therefore do not need prolonged thromboprophylaxis. This hypothesis was tested in this paper. METHODS: All patients who underwent laparoscopic colorectal surgery in our Colorectal Surgical Unit in the period from June 1991 until January 2010 were entered into a prospective database. The entire database was reviewed, and incidence of thromboembolic disease and significant bleeding complications were noted. RESULTS: Three thousand, three hundred sixty-four patients were laparoscopically operated on for colorectal disease and were entered in the database. Two thousand, one hundred twenty-seven patients were operated on for benign disease; 1,230, for colorectal cancer, and four, for other malignancies. Two deep venous thromboses were encountered (0.059%), and ten patients had pulmonary embolism (0.30%). The combined venous thromboembolism (VTE) risk for the overall group of patients undergoing laparoscopic colorectal operations is 0.36%. The combined VTE risk was 0.57% (7/1,230) in patients with colorectal cancer and 0.24% (5/2,127) in patients with benign disease (p = 0.118). Bleeding complications occurred in 44 patients (1.3%). CONCLUSIONS: In our group, the combined VTE risk for the overall group of patients undergoing laparoscopic colorectal operations is 0.36%. Therefore, we postulate that the prolonged use of thromboprophylaxis is not indicated in the vast majority of patients undergoing laparoscopic colorectal surgery. In particular, patients undergoing laparoscopic resections for benign disease and without other risk factors have such a low VTE risk that prolonged prophylaxis is probably not warranted.