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Guidelines are increasingly determining the decision process in day-to-day clinical work. Guidelines describe the current best possible standard in diagnostics and therapy. They should be developed by an international panel of experts, whereby alongside individual experience, above all, the results of comparative studies are decisive. According to the results of high-ranking scientific studies published in peer-reviewed journals, statements and recommendations are formulated, and these are graded strictly according to the criteria of evidence-based medicine. Guidelines can therefore be valuable in helping particularly the young surgeon in his or her day-to-day work to find the best decision for the patient when confronted with a wide and confusing range of options. However, even experienced surgeons benefit because by virtue of a heavy workload and commitment, they often find it difficult to keep up with the ever-increasing published literature. All guidelines require regular updating, usually every 3 years, in line with progress in the field. The current Guidelines focus on technique and perioperative management of laparoscopic ventral hernia repair and constitute the first comprehensive guidelines on this topic. In this issue of Surgical Endoscopy, the first part of the Guidelines is published including sections on basics, indication for surgery, perioperative management, and key points of technique. The next part (Part 2) of the Guidelines will address complications and comparisons between open and laparoscopic techniques. Part 3 will cover mesh technology, hernia prophylaxis, technique-related issues, new technologic developments, lumbar and other unusual hernias, and training/education.

The drug praziquantel (PZQ) is the key clinical therapy for treating schistosomiasis and other infections caused by parasitic flatworms. A schistosome target for PZQ was recently identified— a transient receptor potential ion channel in the melastatin subfamily (TRPMPZQ)—however, little is known about the properties of TRPMPZQ in other parasitic flatworms. Here, TRPMPZQ orthologs were scrutinized from all currently available parasitic flatworm genomes. TRPMPZQ is present in all parasitic flatworms, and the consensus PZQ binding site was well conserved. Functional profiling of trematode, cestode, and a free-living flatworm TRPMPZQ ortholog revealed differing sensitives (~300-fold) of these TRPMPZQ channels toward PZQ, which matched the varied sensitivities of these different flatworms to PZQ. Three loci of variation were defined across the parasitic flatworm TRPMPZQ pocketome with the identity of an acidic residue in the TRP domain acting as a gatekeeper residue impacting PZQ residency within the TRPMPZQ ligand binding pocket. In trematodes and cyclophyllidean cestodes, which display high sensitivity to PZQ, this TRP domain residue is an aspartic acid which is permissive for potent activation by PZQ. However, the presence of a glutamic acid residue found in other parasitic and free-living flatworm TRPMPZQ was associated with lower sensitivity to PZQ. The definition of these different binding pocket architectures explains why PZQ shows high therapeutic effectiveness against specific fluke and tapeworm infections and will help the development of better tailored therapies toward other parasitic infections of humans, livestock, and fish.

Control of the neglected tropical disease schistosomiasis relies almost entirely on praziquantel (PZQ) monotherapy. How PZQ clears parasite infections remains poorly understood. Many studies have examined the effects of PZQ on worms cultured in vitro , observing outcomes such as muscle contraction. However, conditions worms are exposed to in vivo may vary considerably from in vitro experiments given the short half-life of PZQ and the importance of host immune system engagement for drug efficacy in animal models. Here, we investigated the effects of in vivo PZQ exposure on Schistosoma mansoni . Measurement of pro-apoptotic caspase activation revealed that worm death occurs only after parasites shift from the mesenteric vasculature to the liver, peaking 24 hours after drug treatment. This indicates that PZQ is not directly schistocidal, since PZQ’s half-life is ~2 hours in humans and ~30 minutes in mice, and focuses attention on parasite interactions with the host immune system following the shift of worms to the liver. RNA-Seq of worms harvested from mouse livers following sub-lethal PZQ treatment revealed drug-evoked changes in the expression of putative immunomodulatory and anticoagulant gene products. Several of these gene products localized to the schistosome esophagus and may be secreted into the host circulation. These include several Kunitz-type protease inhibitors, which are also found in the secretomes of other blood feeding animals. These transcriptional changes may reflect mechanisms of parasite immune-evasion in response to chemotherapy, given the role of complement-mediated attack and the host innate/humoral immune response in parasite elimination. One of these isoforms, SmKI-1, has been shown to exhibit immunomodulatory and anti-coagulant properties. These data provide insight into the effect of in vivo PZQ exposure on S . mansoni , and the transcriptional response of parasites to the stress of chemotherapy.

Given the worldwide burden of neglected tropical diseases, there is ongoing need to develop novel anthelmintic agents to strengthen the pipeline of drugs to combat these burdensome infections. Many diseases caused by parasitic flatworms are treated using the anthelmintic drug praziquantel (PZQ), employed for decades as the key clinical agent to treat schistosomiasis. PZQ activates a flatworm transient receptor potential (TRP) channel within the melastatin family (TRPM PZQ ) to mediate sustained Ca 2+ influx and worm paralysis. As a druggable target present in many parasitic flatworms, TRPM PZQ is a promising target for a target-based screening campaign with the goal of discovering novel regulators of this channel complex. Here, we have optimized methods to miniaturize a Ca 2+ -based reporter assay for Schistosoma mansoni TRPM PZQ ( Sm .TRPM PZQ ) activity enabling a high throughput screening (HTS) approach. This methodology will enable further HTS efforts against Sm .TRPM PZQ as well as other flatworm ion channels. A pilot screen of ~16,000 compounds yielded a novel activator of Sm .TRPM PZQ , and numerous potential blockers. The new activator of Sm .TRPM PZQ represented a distinct chemotype to PZQ, but is a known chemical entity previously identified by phenotypic screening. The fact that a compound prioritized from a phenotypic screening campaign is revealed to act, like PZQ, as an Sm .TRPM PZQ agonist underscores the validity of TRPM PZQ as a druggable target for antischistosomal ligands.

Purpose Chronic inguinodynia is one of the most frequent complications after groin herniorrhaphy. We investigated the retroperitoneal anatomy of the iliohypogastric, ilioinguinal, genitofemoral, and lateral femoral cutaneous nerve to prevent direct nerve injury during hernia repairs and to find the most advantageous approach for posterior triple neurectomy. Methods We dissected the inguinal nerves in 30 human anatomic specimens bilaterally. The distances from each nerve and their entry points in the abdominal wall were measured in relation to the posterior superior iliac spine, anterior superior iliac spine, and the midpoint between the two iliac spines on the iliac crest. We evaluated our findings by creating high-resolution summation images. Results The courses of the iliohypogastric and ilioinguinal nerve are most consistent on the anterior surface of the quadratus lumborum muscle. The genitofemoral nerve always runs on the psoas muscle. The entry points of the nerves in the abdominal wall are located as follows: the iliohypogastric nerve is above the iliac crest and lateral from the anterior superior iliac spine, the ilioinguinal nerve is with great variability, either above or below the iliac crest and lateral from the anterior superior iliac spine, the genital branch is around the internal inguinal ring, the femoral branch is either cranial or caudal to the iliopubic tract, and the lateral femoral cutaneous nerve is either medial or lateral to the anterior superior iliac spine. Conclusion Nerve injury during inguinal hernia repairs can be avoided by taking the topographic anatomy of the inguinal nerves into consideration. The most advantageous plane to look for the iliohypogastric and ilioinguinal nerve during posterior neurectomy is on the anterior surface of the quadratus lumborum muscle. For the surgical treatment of severe chronic inguinodynia, especially after posterior open or endoscopic mesh repair (TAPP/TEP), the retroperitoneoscopic or open retroperitoneal approach for posterior triple neurectomy can be considered.

The transition from subduction in Cascadia to the transform Queen Charlotte fault along western Canada is often drawn as a subduction zone, yet recent studies of GPS and earthquake data from northern Vancouver Island are not consistent with that model. In this paper we synthesize seismic reflection and gravity interpretations with microseismicity data in order to test models of (1) microplate subduction and (2) reorganization of the preexisting strike‐slip plate boundary. We focus on the critical region of outer Queen Charlotte Sound and the adjacent offshore. On much of the continental shelf, several million years of subsidence above thin crust are a counterindicator for subduction. An undated episode of compression uplifted the southernmost shelf, but subsidence patterns offshore show that recent subduction is unlikely to be responsible. Previously unremarked near‐vertical faults and a mix of extensional and compressional faults offshore indicate that strike‐slip faulting has been a significant mode of deformation. Seismicity in the last 18 years is dominantly strike‐slip and shows large amounts of moment release on the Revere‐Dellwood fault and its overlap with the Queen Charlotte fault. The relative plate motion between the Pacific and North American plates rotated clockwise ∼6 Ma and appears to have triggered formation of an evolving array of structures. We suggest that the paleo‐Queen Charlotte fault which had defined this continental margin retreated northward as offshore distributed shear and the newly formed Revere Dellwood fault propagated to the northwest.

Offshore basalts, most commonly found as oceanic crust formed at mid-ocean ridges, are estimated to offer an almost unlimited reservoir for CO2 sequestration and are regarded as one of the most durable locations for carbon sequestration since injected CO2 will mineralize, forming carbonate rock. As part of the Solid Carbon project, the potential of the Cascadia Basin, about 200 km off the west coast of Vancouver Island, Canada, is investigated as a site for geological CO2 sequestration. In anticipation of a demonstration proposed to take place, it is essential to assess the tendency of geologic faults in the area to slip in the presence of CO2 injection, potentially causing seismic events. To understand the viability of the reservoir, a quantitative risk assessment of the proposed site area was conducted. This involved a detailed characterization of the proposed injection site to understand baseline stress and pressure conditions and identify individual faults or fault zones with the potential to slip and thereby generate seismicity. The results indicate that fault slip potential is minimal (less than 1%) for a constant injection of up to ~2.5 MT/yr. This is in part due to the thickness of the basalt aquifer and its permeability. The results provide a reference for assessing the potential earthquake risk from CO2 injection in similar ocean basalt basins.

This case describes the endovascular treatment of a 55-year old female with a ruptured portal vein pseudoaneurysm secondary to a large stomach ulcer resulting in massive active hemorrhage into the adjacent stomach. This patient presented with persistent hypotension secondary to chronic GI blood loss and simultaneous septic shock. After an abrupt drop in blood pressure, the patient arrived in the angiography suite where the ruptured pseudoaneurysm was apparent on portal venogram. Emergent stent assisted coil embolization was performed to stabilize the patient and treat the portal vein pseudoaneurysm. To our knowledge, this case presents the only portal vein pseudoaneurysm secondary to a gastric ulcer. Level of Evidence  Level 4, Case-report