Robotic assisted surgery reduces ergonomic risk during minimally invasive colorectal resection: the VOLCANO randomised controlled trial.

PURPOSE: Minimally invasive surgery benefits patients but poor operating ergonomics causes musculoskeletal injuries in surgeons. This randomised controlled trial aims to assess whether robotic-assisted surgery with the open-console Versius® system can reduce surgeons' ergonomic risks during major colorectal resections. METHODS: Prospectively registered at ClinicalTrials.gov (NCT05262296) in March 2022. Adult patients requiring a minimally invasive colorectal resection were potentially eligible. Photographs taken at 2-min intervals were analysed using the objective Rapid Entire Body Assessment (REBA) posture analysis scale to calculate intraoperative surgeon ergonomic risk. Secondary outcomes included team communication (Oxford NOTECHS II), surgeon cognitive strain (modified NASA-TLX scale), and clinical outcomes. RESULTS: Sixty patients were randomised in a 2:1 ratio (40 robot, 20 laparoscopic). Mean age was 65yrs and 34 (57%) were male. Body Mass Index did not differ between the 2 groups (overall mean 29.0 ± 5) and there were equal proportions of left and right-colonic resections. REBA was significantly lower in the robotic arm (median robot REBA score 3 vs lap REBA 5 [p < 0.001]), equating to an injury risk category drop from "medium" to "low risk". There were no significant differences in team communication, operative duration, or patient outcomes. Surgeon cognitive strain was lower in robotic cases (mean robot 32.4 ± 10.3 vs lap 45.6 ± 14.3 [p < 0.001]). CONCLUSIONS: This trial demonstrates that robotic surgery with an open-console system reduces ergonomic risk scores and cognitive strain during colorectal resections, with no apparent detriment to team communication. This may therefore be a safe & feasible solution to the increasing problem of work-related musculoskeletal injuries in surgeons.

Mitigation of Cardiovascular Disease and Toxicity through NRF2 Signalling.

Cardiovascular toxicity and diseases are phenomena that have a vastly detrimental impact on morbidity and mortality. The pathophysiology driving the development of these conditions is multifactorial but commonly includes the perturbance of reactive oxygen species (ROS) signalling, iron homeostasis and mitochondrial bioenergetics. The transcription factor nuclear factor erythroid 2 (NFE2)-related factor 2 (NRF2), a master regulator of cytoprotective responses, drives the expression of genes that provide resistance to oxidative, electrophilic and xenobiotic stresses. Recent research has suggested that stimulation of the NRF2 signalling pathway can alleviate cardiotoxicity and hallmarks of cardiovascular disease progression. However, dysregulation of NRF2 dynamic responses can be severely impacted by ageing processes and off-target toxicity from clinical medicines including anthracycline chemotherapeutics, rendering cells of the cardiovascular system susceptible to toxicity and subsequent tissue dysfunction. This review addresses the current understanding of NRF2 mechanisms under homeostatic and cardiovascular pathophysiological conditions within the context of wider implications for this diverse transcription factor.

Stem cell models as an in vitro model for predictive toxicology.

Adverse drug reactions (ADRs) are the unintended side effects of drugs. They are categorised as either predictable or unpredictable drug-induced injury and may be exhibited after a single or prolonged exposure to one or multiple compounds. Historically, toxicology studies rely heavily on animal models to understand and characterise the toxicity of novel compounds. However, animal models are imperfect proxies for human toxicity and there have been several high-profile cases of failure of animal models to predict human toxicity e.g. fialuridine, TGN1412 which highlight the need for improved predictive models of human toxicity. As a result, stem cell-derived models are under investigation as potential models for toxicity during early stages of drug development. Stem cells retain the genotype of the individual from which they were derived, offering the opportunity to model the reproducibility of rare phenotypes in vitro Differentiated 2D stem cell cultures have been investigated as models of hepato- and cardiotoxicity. However, insufficient maturity, particularly in the case of hepatocyte-like cells, means that their widespread use is not currently a feasible method to tackle the complex issues of off-target and often unpredictable toxicity of novel compounds. This review discusses the current state of the art for modelling clinically relevant toxicities, e.g. cardio- and hepatotoxicity, alongside the emerging need for modelling gastrointestinal toxicity and seeks to address whether stem cell technologies are a potential solution to increase the accuracy of ADR predictivity in humans.

Colonization and degradation of polyhydroxyalkanoates by lipase-producing bacteria.

Biodegradation of short-chain-length polyhydroxyalkanoates (scl-PHAs) and medium-chain-length polyhydroxyalkanoates (mcl-PHAs) was studied using 2 bacteria, Pseudomonas chlororaphis and Acinetobacter lwoffii, which secrete an enzyme, or enzymes, with lipase activity. These bacteria produced clear zones of depolymerization on Petri plates containing colloidal solutions of PHA polymers with different monomer compositions. Lipase activity in these bacteria was measured using p-nitrophenyl octanoate as a substrate. In liquid medium, scl-PHA (e.g., PHBV) and mcl-PHA (e.g., PHO) films were used as the sole carbon source for growth, and after 7 days, 5%-18% loss in mass of PHA films was observed. Scanning electron microscopy of these films revealed bacterial colonization of the polymers, with cracks and pitting in the film surfaces. Degradation of polymers released 3-hydroxyhexanoate, 3-hydroxyoctanoate, and 3-hydroxydecanoate monomers into the liquid medium, depending on the starting polymer. Genes encoding secretory lipases, with amino acid consensus sequences for lipase boxes and oxyanion holes, were identified in the genomes of P. chlororaphis and A. lwoffii. Although amino acid consensus sequences for lipase boxes and oxyanion holes are also present in PHA depolymerases identified in the genomes of other PHA-degrading bacteria, the P. chlororaphis and A. lwoffii lipases had low homology with these depolymerases.

Global phosphoproteomic profiling reveals perturbed signaling in a mouse model of dilated cardiomyopathy.

Phospholamban (PLN) plays a central role in Ca2+ homeostasis in cardiac myocytes through regulation of the sarco(endo)plasmic reticulum Ca2+-ATPase 2A (SERCA2A) Ca2+ pump. An inherited mutation converting arginine residue 9 in PLN to cysteine (R9C) results in dilated cardiomyopathy (DCM) in humans and transgenic mice, but the downstream signaling defects leading to decompensation and heart failure are poorly understood. Here we used precision mass spectrometry to study the global phosphorylation dynamics of 1,887 cardiac phosphoproteins in early affected heart tissue in a transgenic R9C mouse model of DCM compared with wild-type littermates. Dysregulated phosphorylation sites were quantified after affinity capture and identification of 3,908 phosphopeptides from fractionated whole-heart homogenates. Global statistical enrichment analysis of the differential phosphoprotein patterns revealed selective perturbation of signaling pathways regulating cardiovascular activity in early stages of DCM. Strikingly, dysregulated signaling through the Notch-1 receptor, recently linked to cardiomyogenesis and embryonic cardiac stem cell development and differentiation but never directly implicated in DCM before, was a prominently perturbed pathway. We verified alterations in Notch-1 downstream components in early symptomatic R9C transgenic mouse cardiomyocytes compared with wild type by immunoblot analysis and confocal immunofluorescence microscopy. These data reveal unexpected connections between stress-regulated cell signaling networks, specific protein kinases, and downstream effectors essential for proper cardiac function.

Expression and enzyme activity of cytochrome P450 enzymes CYP3A4 and CYP3A5 in human skin and tissue-engineered skin equivalents.

CYP3A4 and CYP4A5 share specificity for a wide range of xenobiotics with the CYP3 subfamily collectively involved in the biotransformation of approximately 30% of all drugs. CYP3A4/5 mRNA transcripts have been reported in the skin, yet knowledge of their protein expression and function is lacking. In this study, we observed gene and protein expression of CYP3A4/5 in both human skin and tissue-engineered skin equivalents (TESEs), and enzyme activity was detected using the model substrate benzyl-O-methyl-cyanocoumarin. Mass spectrometric analysis of TESE lysates following testosterone application revealed a time-dependent increase in metabolite production, confirming the functional expression of these enzymes in skin.

Metformin increases degradation of phospholamban via autophagy in cardiomyocytes.

Phospholamban (PLN) is an effective inhibitor of the sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA). Here, we examined PLN stability and degradation in primary cultured mouse neonatal cardiomyocytes (CMNCs) and mouse hearts using immunoblotting, molecular imaging, and [(35)S]methionine pulse-chase experiments, together with lysosome (chloroquine and bafilomycin A1) and autophagic (3-methyladenine and Atg5 siRNA) antagonists. Inhibiting lysosomal and autophagic activities promoted endogenous PLN accumulation, whereas accelerating autophagy with metformin enhanced PLN degradation in CMNCs. This reduction in PLN levels was functionally correlated with an increased rate of SERCA2a activity, accounting for an inotropic effect of metformin. Metabolic labeling reaffirmed that metformin promoted wild-type and R9C PLN degradation. Immunofluorescence showed that PLN and the autophagy marker, microtubule light chain 3, became increasingly colocalized in response to chloroquine and bafilomycin treatments. Mechanistically, pentameric PLN was polyubiquitinylated at the K3 residue and this modification was required for p62-mediated selective autophagy trafficking. Consistently, attenuated autophagic flux in HECT domain and ankyrin repeat-containing E3 ubiquitin protein ligase 1-null mouse hearts was associated with increased PLN levels determined by immunoblots and immunofluorescence. Our study identifies a biological mechanism that traffics PLN to the lysosomes for degradation in mouse hearts.

Synthesis of polyhydroxyalkanoates (PHAs) from vegetable oils and free fatty acids by wild-type and mutant strains of Pseudomonas chlororaphis.

Pseudomonas chlororaphis PA23 was isolated from soybean roots as a plant-growth-promoting rhizobacterium. This strain secretes a wide range of compounds, including the antibiotics phenazine-1-carboxylic acid (PCA), pyrrolnitrin, and 2-hydroxyphenazine. We have determined that P. chlororaphis PA23 can synthesize medium-chain-length polyhydroxyalkanoate (PHA) polymers utilizing free fatty acids, such as octanoic acid and nonanoic acid, as well as vegetable oils as sole carbon sources. Genome analysis identified a pha operon containing 7 genes in P. chlororaphis PA23 that were highly conserved. A nonpigmented strain that does not synthesize PCA, P. chlororaphis PA23-63, was also studied for PHA production. Pseudomonas chlororaphis PA23-63 produced 2.42-5.14 g/L cell biomass and accumulated PHAs from 11.7% to 32.5% cdm when cultured with octanoic acid, nonanoic acid, fresh canola oil, waste canola fryer oil, or biodiesel-derived waste free fatty acids under batch culture conditions. The subunit composition of the PHAs produced from fresh canola oil, waste canola fryer oil, or biodiesel-derived free fatty acids did not differ significantly. Addition of octanoic acid and nonanoic acid to canola oil cultures increased PHA production, but addition of glucose did not. PHA production in the phz mutant, P. chlororaphis PA23-63, was greater than that in the parent strain.

The Future of Emergency Surgery.

Introduction: Over the past three decades, there has been a recognised need for emergency surgery (ES). Studies of ES have demonstrated variation in patient outcomes depending on admission time or day. ES as a subspecialty is still under consideration in Europe despite being recognised as such in the US. This article reviews this need and addresses the issues required to develop ES as a separate surgical subspecialty in Europe. METHOD: A survey on ES was developed by the Educational Committee of the European Society for Trauma and Emergency Surgery (ESTES) and sent to all ESTES members with 102 responses received. Results: Of the responses, 93.1% had completed training. 75.3% of respondents report that ES should be a recognised subspecialty and 79% report that ES is capable of offering a rewarding career. 90% report that ES should have dedicated post-graduate training programme with 69.8% in agreement that dedicated emergency surgeons have improved outcomes following ES. CONCLUSION: Developing ES as a subspecialty in Europe would improve patient outcomes and facilitate resource allocation. This advancement is, however, still in its infancy and its evolution would require overhaul of our current European system, training methods and understanding of the role of emergency surgeons in ES.

Apps in Trauma and Emergency Surgery.

Background: As physicians, Mobile smartphones, laptops and tablets are now an integral part of our day to day activities including personal communications as well as our routine clinical practice. Methods: A digital survey was designed to explore the usage of mobile smartphones and the associated apps among surgeons in Trauma and Emergency departments. It was sent to 850 members of the European Society for Trauma and Emergency Surgery. Results: A total of 91 responses were received with 60.4% aged between 35 and 54 years. Only 24.1%of respondents found the available apps extremely useful in their practice, however 75.9% of participants agreed on not being able to identify a certain good application to rely on. CONCLUSION: Despite the widespread use of smartphones among doctors of different grades and specialties, there is a preference shown towards the use of instant messenger apps and the use of the camera for clinical photos. The usefulness of current available apps appears to be limited due to the absence of a regulating body to check the validity of data and peer review the contents of apps leaving a huge responsibility on the individual doctor using the app to rely on its results.

Effects of impurities in biodiesel-derived glycerol on growth and expression of heavy metal ion homeostasis genes and gene products in Pseudomonas putida LS46.

Biodiesel production-derived waste glycerol (WG) was previously investigated as potential carbon source for medium chain length polyhydroxyalkanoate (mcl-PHA) production by Pseudomonas putida LS46. In this study, we evaluated the effect of impurities in the WG on P. putida LS46 physiology during exponential growth and corresponding changes in transcription and protein expression profiles compared with cells grown on pure, reagent grade glycerol. High concentration of metal ions, such as Na(+), and numbers of heavy metals ion, such as copper, ion, zinc, were detected in biodiesel-derived WG. Omics analysis from the corresponding cultures suggested altered expression of genes involved in transport and metabolism of ammonia and heavy metal ions. Expression of three groups of heavy metal homeostasis genes was significantly changed (mostly upregulated) in WG cultures and included the following: copper-responded cluster 1 and 2 genes, primarily containing cusABC; two copies of copAB and heavy metal translocating P-type ATPase; Fur-regulated, TonB-dependent siderophore receptor; and several cobalt/zinc/cadmium transporters. Expression of these genes suggests regulation of intracellular concentrations of heavy metals during growth on biodiesel-derived glycerol. Finally, a number of genes involved in adapting to, or metabolizing free fatty acids and other nonheavy metal contaminants, such as Na(+), were also upregulated in P. putida LS46 grown on biodiesel-derived glycerol.

Study protocol for the randomised controlled trial: Ketamine augmentation of ECT to improve outcomes in depression (Ketamine-ECT study).

BACKGROUND: There is a robust empirical evidence base supporting the acute efficacy of electroconvulsive therapy (ECT) for severe and treatment resistant depression. However, a major limitation, probably contributing to its declining use, is that ECT is associated with impairment in cognition, notably in anterograde and retrograde memory and executive function. Preclinical and preliminary human data suggests that ketamine, used either as the sole anaesthetic agent or in addition to other anaesthetics, may reduce or prevent cognitive impairment following ECT. A putative hypothesis is that ketamine, through antagonising glutamate receptors, protects from excess excitatory neurotransmitter stimulation during ECT. The primary aim of the ketamine-ECT study is to investigate whether adjunctive ketamine can attenuate the cognitive impairment caused by ECT. Its secondary aim is to examine if ketamine increases the speed of clinical improvement with ECT. METHODS/DESIGN: The ketamine ECT study is a multi-site randomised, placebo-controlled, double blind trial. It was originally planned to recruit 160 moderately to severely depressed patients who had been clinically prescribed ECT. This recruitment target was subsequently revised to 100 patients due to recruitment difficulties. Patients will be randomly allocated on a 1:1 basis to receive either adjunctive ketamine or saline in addition to standard anaesthesia for ECT. The primary neuropsychological outcome measure is anterograde verbal memory (Hopkins Verbal Learning Test-Revised delayed recall task) after 4 ECT treatments. Secondary cognitive outcomes include verbal fluency, autobiographical memory, visuospatial memory and digit span. Efficacy is assessed using observer and self-report efficacy measures of depressive symptomatology. The effects of ECT and ketamine on cortical activity during cognitive tasks will be studied in a sub-sample using functional near-infrared spectroscopy (fNIRS). DISCUSSION: The ketamine-ECT study aims to establish whether or not adjunctive ketamine used together with standard anaesthesia for ECT will significantly reduce the adverse cognitive effects observed after ECT. Potential efficacy benefits of increased speed of symptom improvement and a reduction in the number of ECT treatments required will also be assessed, as will safety and tolerability of adjunctive ketamine. This study will provide important evidence as to whether adjunctive ketamine is routinely indicated for ECT given for depression in routine NHS clinical practice. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN14689382 (assigned 30/07/2012); EudraCT Number: 2011-005476-41.

Proteomic analysis of human fetal atria and ventricle.

In this study we carried out a mass spectrometry-based proteome analysis of human fetal atria and ventricles. Heart protein lysates were analyzed on the Q-Exactive mass spectrometer in biological triplicates. Protein identification using MaxQuant yielded a total of 2754 atrial protein groups (91%) and 2825 ventricular protein groups (83%) in at least 2 of the 3 runs with ≥ 2 unique peptides. Statistical analyses using fold-enrichment (>2) and p-values (≤ 0.05) selected chamber-enriched atrial (134) and ventricular (81) protein groups. Several previously characterized cardiac chamber-enriched proteins were identified in this study including atrial isoform of myosin light chain 2 (MYL7), atrial natriuretic peptide (NPPA), connexin 40 (GJA5), and peptidylglycine alpha-amidating monooxygenase (PAM) for atria, and ventricular isoforms of myosin light chains (MYL2 and MYL3), myosin heavy chain 7 (MYH7), and connexin 43 (GJA1) for ventricle. Our data was compared to in-house generated and publicly available human microarrays, several human cardiac proteomes, and phenotype ontology databases.

Studies on salinization in Haryana soils on free-living nitrogen-fixing bacterial populations and their activity.

A total of 26 soil samples from saline soils of Haryana were collected. Based on their electrical conductivity (EC) values, which varied from 1.04 to 21.00 dS m(-1), the soils were categorized into non-saline soils (EC 0-2 dS m(-1)), weakly saline soils (EC 2-4 dS m(-1)), saline soils (EC 4-8 dS m(-1)), strongly saline soils (EC 8-16 dS m(-1)), and very strongly saline soils (EC >16 dS m(-1)). The pH values of these soil samples ranged from 6.03 to 8.62, while organic C, total N, and available P were in the range of 0.06-0.94%, 0.07-0.15%, and 0.11-0.29 µg g(-1) soil, respectively. As a measure of the impact of salinity on free-living N(2) fixers and their activity, the total bacterial populations on four media (Jensen's nitrogen-free medium, malate medium, Burk's medium, and soil extract agar medium) decreased from 6.12 to 3.70 log CFU g(-1) soil with increasing salinity level. PCR amplification of the nifH region of the DNA from 234 selected morphotypes from all the media showed the presence of nifH in 71 isolates. Out of these, 37% of the isolates were obtained using Jensen's medium; 35, 28, and 21% of the isolates were obtained using soil extract medium, Burk's medium, and malate medium, respectively. The majority of the free-living N(2) fixers (67%) were Gram negative. Apart from the acetylene reduction assay (ARA) activity in these isolates, other beneficial traits like ammonia excretion and indole acetic acid (IAA) production were also present. A decreasing trend in the activities was observed with increasing salinity levels. Isolates JN6, BP8, and MJ4 showed the highest ARA activity, ammonia excretion, and IAA production. The performance of isolates like BNC2 with good ARA activity, ammonia excretion, and IAA production and isolated from a very strongly saline soil should be further evaluated under high-saline conditions.

A Study to Assess Biochemical Profile of Tobacco Chewers with Chewing Habit Over a Period of 10 Years.

The study was conducted to evaluate the systemic adverse effects of smokeless tobacco (SLT) on hematological as well as other biochemical parameters and find out if any correlation between them which may be worthy of creating awareness among the masses against its usage. The current observational study was carried out among 250 tobacco chewers, and complete hemogram, LFT profile, and electrolyte profile were studied. The mean values of hemoglobin (Hb) gram % was 12.74 ± 1.6, total leucocyte count (TLC/cu mm) is 6608.33 ± 1752.083, and platelet count lakh cell/cu mm is 2.55 ±0.806. The mean values of Na+ mmol/1 of the S. electrolyte profile was 132 ± 18.05 and K+ mmol/1 was 3.89 ± 0.538. The study deliberates imperative perception into smokeless tobacco-mediated effects on body systemic functions and reports a crucial part into SLT-mediated effects on biochemical profile and metabolism which can be revealed in promoting tobacco cessation.

Rootstock scion interaction studies on various horticultural attributes of pomato grafts under protected structures.

Pomato is a horticultural wonder plant, as tomato and potato can be produced from a single plant. This experiment explored the influence of diverse graft combinations of tomato scions grafted onto potato rootstocks on various growth and yield-attributing traits. The investigation outcomes confirmed the significantly positive influence of scion grafted onto rootstock on various yielding attributes of tomato and potato harvested from pomato grafts. Scion "Rakshita" grafted onto the rootstock of Kufri Himalini had the maximum fruit length. In contrast, the fruits harvested from the graft combination of Avtar grafted onto Kufri Khyati had the maximum number of fruits per cluster and the number of fruits per plant. The highest average fruit weight, fruit yield per meter square, and total fruit yield quintal per hectare were recorded with control "Avtar. The longest harvest duration was noticed with the graft combination of Heemsohna grafted onto Kufri Himalini. Moreover, on, rootstock Kufri Himalini with scion Rakshita resulted in maximum tuber length, and average tuber weight, while Kufri Himalini with Avtar had maximum fruit width. The maximum number of tubers per plant was also noticed with Kufri Pukhraj with Palam Tomato hybrid -1. The potato harvested from the rootstock of Kufri Pukhraj with Avtar had the highest tuber yield per plant, total tuber yield quintal per hectare, and tuber equivalent yield. The highest survival percentage of grafted plants was noted in Heemsohna onto Kufri Jyoti. In context to the cumulative yield of tomato fruits and potato tubers obtained from the pomato graft was found to be incremented in grafts of Avtar grafted onto Kufri Pukhraj followed by Rakshita grafted onto Kufri Rakshita, which also resulted in the maximum benefit-cost ratio with highest net return and gross return. The graft combination of scion Avtar and Rakshita onto Rootstock Kufri Pukhraj resulted in a positive increment in yield attributing traits of the pomato plant than of control of un-grafted tomato and potato.

Identification and characterisation of functional Kir6.1-containing ATP-sensitive potassium channels in the cardiac ventricular sarcolemmal membrane.

BACKGROUND AND PURPOSE: The canonical Kir6.2/SUR2A ventricular KATP channel is highly ATP-sensitive and remains closed under normal physiological conditions. These channels activate only when prolonged metabolic compromise causes significant ATP depletion and then shortens the action potential to reduce contractile activity. Pharmacological activation of KATP channels is cardioprotective, but physiologically, it is difficult to understand how these channels protect the heart if they only open under extreme metabolic stress. The presence of a second KATP channel population could help explain this. Here, we characterise the biophysical and pharmacological behaviours of a constitutively active Kir6.1-containing KATP channel in ventricular cardiomyocytes. EXPERIMENTAL APPROACH: Patch-clamp recordings from rat ventricular myocytes in combination with well-defined pharmacological modulators was used to characterise these newly identified K+ channels. Action potential recording, calcium (Fluo-4) fluorescence measurements and video edge detection of contractile function were used to assess functional consequences of channel modulation. KEY RESULTS: Our data show a ventricular K+ conductance whose biophysical characteristics and response to pharmacological modulation were consistent with Kir6.1-containing channels. These Kir6.1-containing channels lack the ATP-sensitivity of the canonical channels and are constitutively active. CONCLUSION AND IMPLICATIONS: We conclude there are two functionally distinct populations of ventricular KATP channels: constitutively active Kir6.1-containing channels that play an important role in fine-tuning the action potential and Kir6.2/SUR2A channels that activate with prolonged ischaemia to impart late-stage protection against catastrophic ATP depletion. Further research is required to determine whether Kir6.1 is an overlooked target in Comprehensive in vitro Proarrhythmia Assay (CiPA) cardiac safety screens.

Translational analysis of mouse and human placental protein and mRNA reveals distinct molecular pathologies in human preeclampsia.

Preeclampsia (PE) adversely impacts ~5% of pregnancies. Despite extensive research, no consistent biomarkers or cures have emerged, suggesting that different molecular mechanisms may cause clinically similar disease. To address this, we undertook a proteomics study with three main goals: (1) to identify a panel of cell surface markers that distinguish the trophoblast and endothelial cells of the placenta in the mouse; (2) to translate this marker set to human via the Human Protein Atlas database; and (3) to utilize the validated human trophoblast markers to identify subgroups of human preeclampsia. To achieve these goals, plasma membrane proteins at the blood tissue interfaces were extracted from placentas using intravascular silica-bead perfusion, and then identified using shotgun proteomics. We identified 1181 plasma membrane proteins, of which 171 were enriched at the maternal blood-trophoblast interface and 192 at the fetal endothelial interface with a 70% conservation of expression in humans. Three distinct molecular subgroups of human preeclampsia were identified in existing human microarray data by using expression patterns of trophoblast-enriched proteins. Analysis of all misexpressed genes revealed divergent dysfunctions including angiogenesis (subgroup 1), MAPK signaling (subgroup 2), and hormone biosynthesis and metabolism (subgroup 3). Subgroup 2 lacked expected changes in known preeclampsia markers (sFLT1, sENG) and uniquely overexpressed GNA12. In an independent set of 40 banked placental specimens, GNA12 was overexpressed during preeclampsia when co-incident with chronic hypertension. In the current study we used a novel translational analysis to integrate mouse and human trophoblast protein expression with human microarray data. This strategy identified distinct molecular pathologies in human preeclampsia. We conclude that clinically similar preeclampsia patients exhibit divergent placental gene expression profiles thus implicating divergent molecular mechanisms in the origins of this disease.

In vivo and in vitro validation of powdery mildew resistance in garden pea genotypes.

Powdery mildew is one of the serious diseases of garden pea which causes a large number of yield losses. Genetic resistance is quite effective, being cost-effective and environment friendly than fungicide applications. In the present studies an initial attempt has been made to identify resistant genotypes against powdery mildew disease developed from hybridization followed by validation of the disease. The experimental material comprised of 48 genotypes that includes 44 advanced breeding lines was evaluated for powdery mildew incidence in Randomized Complete Block Design with three replications at two locations under field conditions [Palampur (winter 2017-18 and 2018-19) and Kukumseri (summer 2018)] and in vitro at Palampur [detached leaf method and polyhouse conditions]. Ten lines viz., SP7, SN-1, SN-6-1, SN-7-1, SN-2, SN-5-2, SN-6-2, SN-10, SN-21 and SP-281 showed resistant reaction along with check Palam Sumool while 27 lines were identified as moderately resistant in comparison to susceptible check Azad P-1. Besides, six lines namely, SP-2, SP-5, SP-10, SP-24, SA-4 and SP-12-1 gave moderately susceptible reaction along with checks Pb-89 and Palam Priya. Only, SP-19 was categorized as susceptible. The high yielding lines SP-3, SP-6 and SP-22 showed moderately resistant reaction in both natural and artificial conditions. Validation of resistance using molecular markers revealed that neither the parental genotypes nor the progenies possess the er1 gene of JI1559. The er2 linked marker ScOPX-171700 was polymorphic between Palam Sumool and Palam Priya but the marker didn't show polymorphism between er2 harboring line (JI2480). These results suggested that the lines showing resistance under field conditions may have some other genes or alleles for resistance and further confirmation is needed by developing mapping populations with specific gene or gene combinations.

Implementation of robotic hernia surgery using the Versius® system.

This case series aims to demonstrate that hernia surgery is safe and feasible using the Versius® robotic system from CMR Surgical, and to describe the surgical techniques used. It is the first series published using this novel system. Forty-one consecutive hernia repair cases were completed using Versius®, including inguinal and ventral hernias. Data were collected prospectively on a number of pre-, peri-, and postoperative outcomes. Techniques are described for robotic transabdominal preperitoneal repair of inguinal hernia, and intraperitoneal onlay mesh repair of ventral hernia. Thirty-two inguinal and nine ventral hernia repairs were performed over a 12-month period. The population were 88% male with a mean body mass index of 27.4 ± 3.5. There were no conversions to open surgery. Median length of stay was 0 days. Six patients (15%) experienced urinary retention, and there were 2 further minor complications with no major complications, readmissions or reoperations. Use of the Versius® system for robotic hernia surgery is safe, with comparable results to existing robotic systems. Implementation is possible with minimal changes to established surgical techniques.