Hepatic grooves: An observational study at laparoscopic surgery.

BACKGROUND: In traditional descriptions, the upper surface of the liver is smooth and convex, but deep depressions are variants that are present in 5%-40% of patients. We sought to determine the relationship between surface depressions and the diaphragm. AIM: To use exploratory laparoscopy to determine the relationship between surface depressions and the diaphragm. METHODS: An observational study was performed in all patients undergoing laparoscopic upper gastro-intestinal operations between January 1, 2023 and January 20, 2024. A thirty-degree laparoscope was used to inspect the liver and diaphragm. When surface depressions were present, we recorded patient demographics, presence of diaphragmatic bands, rib protrusions and/or any other source of compression during inspection. RESULTS: Of 394 patients, 343 had normal surface anatomy, and 51 (12.9%) had prominent surface depressions on the liver. There was no significant relationship between the presence of surface depressions and gender nor the presence of rib projections. However, there was significant association between the presence of surface depressions and diaphragmatic muscular bands (P < 0.001). CONCLUSION: With these data, the diaphragmatic-band theory has gained increased importance over other theories for surface depressions. Further studies are warranted using cross sectional imaging to confirm relationships with intersectional planes as well as beta-catenin assays in the affected liver parenchyma.

Filamentation of a relativistic proton bunch in plasma.

We show in experiments that a long, underdense, relativistic proton bunch propagating in plasma undergoes the oblique instability, which we observe as filamentation. We determine a threshold value for the ratio between the bunch transverse size and plasma skin depth for the instability to occur. At the threshold, the outcome of the experiment alternates between filamentation and self-modulation instability (evidenced by longitudinal modulation into microbunches). Time-resolved images of the bunch density distribution reveal that filamentation grows to an observable level late along the bunch, confirming the spatiotemporal nature of the instability. We provide a rough estimate of the amplitude of the magnetic field generated in the plasma by the instability and show that the associated magnetic energy increases with plasma density.

Hosing of a Long Relativistic Particle Bunch in Plasma.

Experimental results show that hosing of a long particle bunch in plasma can be induced by wakefields driven by a short, misaligned preceding bunch. Hosing develops in the plane of misalignment, self-modulation in the perpendicular plane, at frequencies close to the plasma electron frequency, and are reproducible. Development of hosing depends on misalignment direction, its growth on misalignment extent and on proton bunch charge. Results have the main characteristics of a theoretical model, are relevant to other plasma-based accelerators and represent the first characterization of hosing.

Evidence for the existence of facilitatory interactions between the dopamine D2 receptor and the oxytocin receptor in the amygdala of the rat. Relevance for anxiolytic actions.

Introduction: The amygdala is a limbic region of high value for understanding anxiety and its treatment. Dopamine D2 receptors (D2Rs) and oxytocin receptors (OXTRs) have both been shown to participate in modulating anxiety involving effects in the amygdala. The goal is to understand if D2R-OXTR heterocomplexes exist in the central amygdala and if, through enhancing allosteric receptor-receptor interactions, may enhance anxiolytic actions. Methods: The methods used involve the shock-probe burying test, the in situ proximity ligation assay (PLA), image acquisition and analysis, and the BRET2 assay. Bilateral cannulas were introduced into the amygdala, and the effects of the coadministration of oxytocin and the D2R-like agonist quinpirole into the amygdala were studied. Results: The combination treatment enhanced the anxiolytic effects compared to the single treatment. The D2R/D3R antagonist raclopride blocked the effects of the combination treatment of oxytocin and the D2R agonist, although oxytocin is regarded as a distinct modulator of fear-mediating anxiolytic effects. In situ PLA results indicate the existence of D2R-OXTR heteroreceptor complexes and/or the co-location of OXTR and D2R within the same cell membrane nanodomains in the central amygdala. With BRET2, evidence is given for the existence of D2R-OXTR heteromers in HEK293 cells upon co-transfection. Discussion: The enhanced behavioral effects observed upon co-treatment with OXTR and D2R agonists may reflect the existence of improved positive receptor-receptor interactions in the putative D2R-OXTR heterocomplexes in certain neuronal populations of the basolateral and central amygdala. The D2R-OXTR heterocomplex, especially upon agonist co-activation in the central amygdala, may open a new pharmacological venue for the treatment of anxiety.

SPR-1/CoREST facilitates the maternal epigenetic reprogramming of the histone demethylase SPR-5/LSD1.

Maternal reprogramming of histone methylation is critical for reestablishing totipotency in the zygote, but how histone-modifying enzymes are regulated during maternal reprogramming is not well characterized. To address this gap, we asked whether maternal reprogramming by the H3K4me1/2 demethylase SPR-5/LSD1/KDM1A, is regulated by the chromatin co-repressor protein, SPR-1/CoREST, in Caenorhabditis elegans and mice. In C. elegans, SPR-5 functions as part of a reprogramming switch together with the H3K9 methyltransferase MET-2. By examining germline development, fertility, and gene expression in double mutants between spr-1 and met-2, as well as fertility in double mutants between spr-1 and spr-5, we find that loss of SPR-1 results in a partial loss of SPR-5 maternal reprogramming function. In mice, we generated a separation of function Lsd1 M448V point mutation that compromises CoREST binding, but only slightly affects LSD1 demethylase activity. When maternal LSD1 in the oocyte is derived exclusively from this allele, the progeny phenocopy the increased perinatal lethality that we previously observed when LSD1 was reduced maternally. Together, these data are consistent with CoREST having a conserved function in facilitating maternal LSD1 epigenetic reprogramming.

Skeletally Immature Patients With Classic Anterior Cruciate Ligament Bone Bruise Patterns Have a Higher Likelihood of Having an Intact Anterior Cruciate Ligament Compared With Skeletally Mature Patients.

BACKGROUND: The incidence of anterior cruciate ligament (ACL) tears in skeletally immature patients with an ACL bone contusion pattern has been sparsely investigated. The purpose of this study is to investigate whether physeal status has an influence on the likelihood of sustaining an ACL tear when classic bipolar ACL bone bruising pattern is present. METHODS: Magnetic resonance imaging reports were queried for "contusion" on all patients between 6 and 22 years between 2015 and 2019. Images were reviewed to denote all intra-articular pathology and the physeal status of the femur and tibia. The primary outcome was the incidence of ACL tears in patients with the presence of bipolar bone contusions. Fischer exact testing was used to determine associations. RESULTS: Of 499 patients included, 269 of those had bipolar bone contusions. Patients with bipolar bone contusions and ACL tears had a shorter duration between injury and imaging date compared with patients with ACL tears without bipolar bone contusions (6.9 vs. 38.6 d, P =0.05). Patients with an open femoral physis had a higher likelihood of having an intact ACL despite the presence of bipolar bone contusions than patients with a closed femoral physis (10.8% vs. 1.0%, P <0.001). Of patients with bipolar bone contusions, those with an intact ACL were younger than patients with an ACL tear (14.6 vs. 16.4, P =0.017). CONCLUSIONS: Although bipolar bone contusions of the central lateral femoral condyle and posterior lateral tibial plateau are typically found after ACL injury, these bipolar contusions can be found concomitantly with an intact ACL and were more often found in relatively younger patients. Patients who have an open femoral physis have a higher likelihood to have an intact ACL despite the presence of bipolar bone contusions compared with patients who have a closed femoral physis. LEVEL OF EVIDENCE: Level IV-cross-sectional.

The Incidence of Posterolateral Tibial Plateau and Central Lateral Femoral Condylar Impaction Fractures in a Pediatric and Young Adult Population.

BACKGROUND: Posterolateral tibial plateau and central lateral femoral condylar impaction fractures are known to occur in the setting of anterior cruciate ligament (ACL) tears. There have been no prior investigations into the incidence and morphology of posterolateral tibial plateau impaction fractures in the setting of ACL injury in a pediatric population. METHODS: Patients between 9 and 22 years of age with knee magnetic resonance imagings (MRIs) performed demonstrating complete or partial ACL tear were included in this study. MRI reports were reviewed to denote the presence of posterior cruciate ligament, medial collateral ligament, or lateral collateral ligament injury, meniscus tears, cartilage lesions. MRIs were reviewed by 2 fellowship-trained orthopaedic surgeons to denote the presence of posterolateral tibial plateau and central lateral femoral condylar impaction fractures and physeal status of femoral and tibial physes. Statistical analysis performed included χ 2 analysis and the Student t testing. RESULTS: A total of 328 patients with a primary ACL tear were identified. The mean age of patients included was 16.5 years (range: 9.0-21.5). The incidence of posterolateral tibial plateau impaction fractures was 83/328 (25.3%) while the incidence of lateral femoral condylar impaction fractures was 119/328 (36.3%). Bipolar impaction fractures occurred in 37/328 (11.3%). Of the 83 tibial impaction fractures identified, 82 were low-grade morphologic subtypes. Patients with lateral tibial plateau impaction fractures were older than those with no fracture (17.2±2.2 vs. 16.3±2.1, P =0.001). Only 3/38 (7.9%) patients with an open tibial physis sustained a tibial plateau impaction fracture compared with 80/290 (27.6%) with a closed tibial physis (χ 2 value: 6.9, P =0.009). There was no difference in proportion of patients with lateral femoral condylar impaction fractures based on femoral physeal status ( P =0.484). CONCLUSION: The incidence of posterolateral tibial plateau impaction fractures in the setting of ACL tear in a pediatric and young adult patient population appears to be lower while lateral femoral condylar impaction fractures occur more frequently when comparing to previously reported incidences found in adult populations in the literature. Furthermore, posterolateral tibial plateau impaction fractures occur less frequently in those with an open proximal tibial physis and high-grade posterolateral tibial plateau bone loss is exceedingly rare in pediatric and young adult patients. Lateral femoral condylar impaction fractures are associated with lateral meniscal tears and medial meniscal ramp lesions. LEVEL OF EVIDENCE: Level IV-cross-sectional study.

Whipple's pancreaticoduodenectomy at a resource-poor, low-volume center in Trinidad and Tobago.

BACKGROUND: Many authorities advocate for Whipple's procedures to be performed in high-volume centers, but many patients in poor developing nations cannot access these centers. We sought to determine whether clinical outcomes were acceptable when Whipple's procedures were performed in a low-volume, resource-poor setting in the West Indies. AIM: To study outcomes of Whipple's procedures in a pancreatic unit in the West Indies over an eight-year period from June 1, 2013 to June 30, 2021. METHODS: This was a retrospective study of all patients undergoing Whipple's procedures in a pancreatic unit in the West Indies over an eight-year period from June 1, 2013 to June 30, 2021. RESULTS: This center performed an average of 11.25 procedures per annum. There were 72 patients in the final study population at a mean age of 60.2 years, with 52.7% having American Society of Anesthesiologists scores ≥ III and 54.1% with Eastern Cooperative Oncology Group scores ≥ 2. Open Whipple's procedures were performed in 70 patients and laparoscopic assisted procedures in 2. Portal vein resection/reconstruction was performed in 19 (26.4%) patients. In patients undergoing open procedures there was 367 ± 54.1 min mean operating time, 1394 ± 656.8 mL mean blood loss, 5.24 ± 7.22 d mean intensive care unit stay and 15.1 ± 9.53 d hospitalization. Six (8.3%) patients experienced minor morbidity, 10 (14%) major morbidity and there were 4 (5.5%) deaths. CONCLUSION: This paper adds to the growing body of evidence that volume alone should not be used as a marker of quality for patients requiring Whipple's procedures. Low volume centers in resource poor nations can achieve good short-term outcomes. This is largely due to the process of continuous, adaptive learning by the entire hospital.

Controlled Growth of the Self-Modulation of a Relativistic Proton Bunch in Plasma.

A long, narrow, relativistic charged particle bunch propagating in plasma is subject to the self-modulation (SM) instability. We show that SM of a proton bunch can be seeded by the wakefields driven by a preceding electron bunch. SM timing reproducibility and control are at the level of a small fraction of the modulation period. With this seeding method, we independently control the amplitude of the seed wakefields with the charge of the electron bunch and the growth rate of SM with the charge of the proton bunch. Seeding leads to larger growth of the wakefields than in the instability case.

Review of minimally invasive pancreas surgery and opinion on its incorporation into low volume and resource poor centres.

Pancreatic surgery has been one of the last areas for the application of minimally invasive surgery (MIS) because there are many factors that make laparoscopic pancreas resections difficult. The concept of service centralization has also limited expertise to a small cadre of high-volume centres in resource rich countries. However, this is not the environment that many surgeons in developing countries work in. These patients often do not have the opportunity to travel to high volume centres for care. Therefore, we sought to review the existing data on MIS for the pancreas and to discuss. In this paper, we review the evolution of MIS on the pancreas and discuss the incorporation of this service into low-volume and resource-poor countries, such as those in the Caribbean. This paper has two parts. First, we performed a literature review evaluating all studies published on laparoscopic and robotic surgery of the pancreas. The data in the Caribbean is examined and we discuss tips for incorporating this operation into resource poor hospital practice. Low pancreatic case volume in the Caribbean, and financial barriers to MIS in general, laparoscopic distal pancreatectomy, enucleation and cystogastrostomy are feasible operations to integrate in to a resource-limited healthcare environment. This is because they can be performed with minimal to no consumables and require an intermediate MIS skillset to complement an open pancreatic surgeon's peri-operative experience.

Caenorhabditis elegans establishes germline versus soma by balancing inherited histone methylation.

Formation of a zygote is coupled with extensive epigenetic reprogramming to enable appropriate inheritance of histone methylation and prevent developmental delays. In Caenorhabditis elegans, this reprogramming is mediated by the H3K4me2 demethylase SPR-5 and the H3K9 methyltransferase, MET-2. In contrast, the H3K36 methyltransferase MES-4 maintains H3K36me2/3 at germline genes between generations to facilitate re-establishment of the germline. To determine whether the MES-4 germline inheritance pathway antagonizes spr-5; met-2 reprogramming, we examined the interaction between these two pathways. We found that the developmental delay of spr-5; met-2 mutant progeny is associated with ectopic H3K36me3 and the ectopic expression of MES-4-targeted germline genes in somatic tissues. Furthermore, the developmental delay is dependent upon MES-4 and the H3K4 methyltransferase, SET-2. We propose that MES-4 prevents crucial germline genes from being repressed by antagonizing maternal spr-5; met-2 reprogramming. Thus, the balance of inherited histone modifications is necessary to distinguish germline versus soma and prevent developmental delay.This article has an associated 'The people behind the papers' interview.

The inhibition of LSD1 via sequestration contributes to tau-mediated neurodegeneration.

Tauopathies are a class of neurodegenerative diseases associated with pathological tau. Despite many advances in our understanding of these diseases, the direct mechanism through which tau contributes to neurodegeneration remains poorly understood. Previously, our laboratory implicated the histone demethylase LSD1 in tau-induced neurodegeneration by showing that LSD1 localizes to pathological tau aggregates in Alzheimer's disease cases, and that it is continuously required for the survival of hippocampal and cortical neurons in mice. Here, we utilize the P301S tauopathy mouse model to demonstrate that pathological tau can exclude LSD1 from the nucleus in neurons. In addition, we show that reducing LSD1 in these mice is sufficient to highly exacerbate tau-mediated neurodegeneration and tau-induced gene expression changes. Finally, we find that overexpressing LSD1 in the hippocampus of tauopathy mice, even after pathology has formed, is sufficient to significantly delay neurodegeneration and counteract tau-induced expression changes. These results suggest that inhibiting LSD1 via sequestration contributes to tau-mediated neurodegeneration. Thus, LSD1 is a promising therapeutic target for tauopathies such as Alzheimer's disease.

Proton Bunch Self-Modulation in Plasma with Density Gradient.

We study experimentally the effect of linear plasma density gradients on the self-modulation of a 400 GeV proton bunch. Results show that a positive or negative gradient increases or decreases the number of microbunches and the relative charge per microbunch observed after 10 m of plasma. The measured modulation frequency also increases or decreases. With the largest positive gradient we observe two frequencies in the modulation power spectrum. Results are consistent with changes in wakefields' phase velocity due to plasma density gradients adding to the slow wakefields' phase velocity during self-modulation growth predicted by linear theory.

Proton-driven plasma wakefield acceleration in AWAKE.

In this article, we briefly summarize the experiments performed during the first run of the Advanced Wakefield Experiment, AWAKE, at CERN (European Organization for Nuclear Research). The final goal of AWAKE Run 1 (2013-2018) was to demonstrate that 10-20 MeV electrons can be accelerated to GeV energies in a plasma wakefield driven by a highly relativistic self-modulated proton bunch. We describe the experiment, outline the measurement concept and present first results. Last, we outline our plans for the future. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Clinical outcomes after major hepatectomy are acceptable in low-volume centers in the Caribbean.

BACKGROUND: Major hepatectomies are routinely performed because they are often the only curative treatment for metastatic liver disease. There has been a trend to concentrate major hepatectomies in referral hospitals that perform these operations at high volumes. These high volume referral centers are usually located in developed countries, but many patients in developing nations are not able to access these centers because of financial limitations, lack of social support and/or travel restrictions. Therefore, local hospitals are often the only options many of these patients have for surgical treatment of metastatic liver disease. This is the situation in many Caribbean countries. AIM: To determine the clinical outcomes after major liver resections in a low-resource hepatobiliary center in the Caribbean. METHODS: We prospectively studied all patients who underwent major liver resections over five years. The following data were extracted: patient demographics, diagnoses, ECOG status, operation performed, post-operative morbidity and mortality. Statistical analyses were performed using SPSS ver 16.0. RESULTS: There were 69 major liver resections performed by two teams at a mean case volume of 13.8 major resections/year. Sixty-nine major hepatic resections were performed for: colorectal liver metastases 40 (58%), non-colorectal metastases 9 (13%), hepatocellular carcinoma 8 (11.6%), ruptured adenomas 4 (5.8%), hilar cholangiocarcinomas 4 (5.8%), hemangiomata 2 (2.9%), trauma 1 (1.5%) and hepatoblastoma 1 (1.5%). Twenty-one patients had at least one complication, for an overall morbidity rate of 30.4%. There were minor complications in 17 (24.6%) patients, major complications in 11 (15.9%) patients and 4 (5.8%) deaths. CONCLUSION: There are unique geographic, political and financial limitations to healthcare delivery in the Caribbean. Nevertheless, clinical outcomes are acceptable in the established, low-volume hepatobiliary centers in the Eastern Caribbean.

Experimental Observation of Proton Bunch Modulation in a Plasma at Varying Plasma Densities.

We give direct experimental evidence for the observation of the full transverse self-modulation of a long, relativistic proton bunch propagating through a dense plasma. The bunch exits the plasma with a periodic density modulation resulting from radial wakefield effects. We show that the modulation is seeded by a relativistic ionization front created using an intense laser pulse copropagating with the proton bunch. The modulation extends over the length of the proton bunch following the seed point. By varying the plasma density over one order of magnitude, we show that the modulation frequency scales with the expected dependence on the plasma density, i.e., it is equal to the plasma frequency, as expected from theory.

Experimental Observation of Plasma Wakefield Growth Driven by the Seeded Self-Modulation of a Proton Bunch.

We measure the effects of transverse wakefields driven by a relativistic proton bunch in plasma with densities of 2.1×10^{14} and 7.7×10^{14} electrons/cm^{3}. We show that these wakefields periodically defocus the proton bunch itself, consistently with the development of the seeded self-modulation process. We show that the defocusing increases both along the bunch and along the plasma by using time resolved and time-integrated measurements of the proton bunch transverse distribution. We evaluate the transverse wakefield amplitudes and show that they exceed their seed value (<15 MV/m) and reach over 300 MV/m. All these results confirm the development of the seeded self-modulation process, a necessary condition for external injection of low energy and acceleration of electrons to multi-GeV energy levels.

Acceleration of electrons in the plasma wakefield of a proton bunch.

High-energy particle accelerators have been crucial in providing a deeper understanding of fundamental particles and the forces that govern their interactions. To increase the energy of the particles or to reduce the size of the accelerator, new acceleration schemes need to be developed. Plasma wakefield acceleration1-5, in which the electrons in a plasma are excited, leading to strong electric fields (so called 'wakefields'), is one such promising acceleration technique. Experiments have shown that an intense laser pulse6-9 or electron bunch10,11 traversing a plasma can drive electric fields of tens of gigavolts per metre and above-well beyond those achieved in conventional radio-frequency accelerators (about 0.1 gigavolt per metre). However, the low stored energy of laser pulses and electron bunches means that multiple acceleration stages are needed to reach very high particle energies5,12. The use of proton bunches is compelling because they have the potential to drive wakefields and to accelerate electrons to high energy in a single acceleration stage13. Long, thin proton bunches can be used because they undergo a process called self-modulation14-16, a particle-plasma interaction that splits the bunch longitudinally into a series of high-density microbunches, which then act resonantly to create large wakefields. The Advanced Wakefield (AWAKE) experiment at CERN17-19 uses high-intensity proton bunches-in which each proton has an energy of 400 gigaelectronvolts, resulting in a total bunch energy of 19 kilojoules-to drive a wakefield in a ten-metre-long plasma. Electron bunches are then injected into this wakefield. Here we present measurements of electrons accelerated up to two gigaelectronvolts at the AWAKE experiment, in a demonstration of proton-driven plasma wakefield acceleration. Measurements were conducted under various plasma conditions and the acceleration was found to be consistent and reliable. The potential for this scheme to produce very high-energy electron bunches in a single accelerating stage20 means that our results are an important step towards the development of future high-energy particle accelerators21,22.