Novel clip applicator for minimally invasive surgery.

BACKGROUND: Ligation clips are used ubiquitously throughout minimally invasive surgery for apposition of tissues. Their size limits their application beyond ligation of small tubular structures. A novel clip and clip applicator that allows for broad-area clamping and rotation has been developed by our team. The primary aim of this study is to provide preliminary data assessing tensile strength of the clip across apposed segments of bowel. METHODS: A comparative study evaluating the maximum load (N) held across two apposed tissues by (a) our novel broad-area clip and (b) a conventional commercial clip was performed. Two sections of porcine bowel were clamped together and the maximum load (N) was measured using a tensile strength material testing machine. A preliminary experiment comparing staple line leak pressures in a porcine model ± clip enforcement of staple line was also conducted. p < 0.05 determined statistical significance. RESULTS: Twenty-four samples (intervention = 15; control = 9) of porcine bowel annealed by surgical clips were tested. The mean maximum force withheld by the bowel and staples was greater for our novel clip design (2.043 ± 0.831 N) than the control clip (1.080 ± 0.466 N, p = 0.004). Ten staple line (intervention = 5; control = 5) pressures of porcine bowel were measured. There was no statistically significant difference between the leak pressures with clip reinforcement (84.8 mmHg; range 71.8-109.8 mmHg), or without (54.1 mmHg; range 26.3-98.9 mmHg). CONCLUSION: These preliminary results suggest that our novel clip is able to withstand higher tensile force across tissues compared to a leading commercial clip. A small preliminary trial of effect on leak pressures demonstrated no statistical significance; however, increasing reliability of staple line deformation may be a clinically important finding. Whilst further iteration of product design and clinical testing is required, this product may occupy an important clinical niche through staple line reinforcement, enterotomy closure and other applications

Patient priorities for research: A focus group study of UK medical cannabis patients

INTRODUCTION: There has yet to be an evaluation of medical cannabis patient preferences with respect to future research. As such, prioritisation of research agendas has been largely driven by academia and industry. The primary aim of this study was to elicit priorities for research from medical cannabis patients in the United Kingdom (UK). METHODS: Patients undergoing active treatment for health conditions with medical cannabis in the UK were invited to take part in focus groups from December 2021 to February 2022. An inductive thematic analysis of responses was performed. Participants also completed a ranking exercise whereby they assigned ten counters (each equivalent to £1 million GBP) to competing research priorities. RESULTS: 30 medical cannabis patients participated across 3 focus groups. The following themes were identified as research priorities: adverse events, comparison between cannabis-based medicinal products, health conditions, pharmacology of cannabis, types of study, healthcare professionals' attitudes, social environment, agriculture and manufacturing, and the cannabis plant. Participants assigned the highest proportion of research funding to 'assessment of effect on specific symptoms' (26 counters; 8.7%). CONCLUSIONS: This study highlighted specific themes within which to focus future research on medical cannabis. Clinically, there was a directive towards ensuring that research is condition- or symptom-specific. Participants also emphasised themes on the social impact of medical cannabis, such as knowledge of medical cannabis among healthcare professionals, stigma, and effects on driving and in the workplace. These findings can guide both research funders and researchers into effectively conducting research which fits within a more patient-centric model

Medical cannabis in multiple sclerosis

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating and neurodegenerative disease of the central nervous system that affects over 100 000 individuals in the UK. The symptoms of MS are heterogenous and correspond to the location of demyelination. However, common symptoms include sensory, motor, cognitive and affective disturbances. While the cornerstone of medical therapy is disease modifying agents, there is an ongoing need to develop symptomatic treatments. Cannabis-based medicinal products (CBMPs), which were partially legalised in the UK in November 2018, have been touted as a potential management option for the associated sequelae of MS. Nabiximols, an oromucosal spray containing cannabidiol and (−)-trans-Δ9-tetrahydrocannabinol, has been extensively evaluated for the treatment of MS-related spasticity. However, unlicensed CBMP formulations are a novel therapeutic class of medications, of which the clinical effects are less well known. Yet, there are promising indications for the use of CBMP in the symptomatic treatment of MS. This article reviews the literature on efficacy and safety of medical cannabis for people with MS

The functional maturation of M cells is dramatically reduced in the Peyer's patches of aged mice

The transcytosis of antigens across the follicle-associated epithelium (FAE) of Peyer's patches by microfold cells (M cells) is important for the induction of efficient immune responses to mucosal antigens. The mucosal immune response is compromised by ageing, but effects on M cells were unknown. We show that M-cell density in the FAE of aged mice was dramatically reduced. As a consequence, aged Peyer's patches were significantly deficient in their ability to transcytose particulate lumenal antigen across the FAE. Ageing specifically impaired the expression of Spi-B and the downstream functional maturation of M cells. Ageing also dramatically impaired C-C motif chemokine ligand 20 expression by the FAE. As a consequence, fewer B cells were attracted towards the FAE, potentially reducing their ability to promote M-cell maturation. Our study demonstrates that ageing dramatically impedes the functional maturation of M cells, revealing an important ageing-related defect in the mucosal immune system's ability to sample lumenal antigens

Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice.

BackgroundSpinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia.MethodsL5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in male Tlr2-/-Tlr3-/-, Tlr4-/-, Tlr5-/-, Myd88-/-, Triflps2, Myd88/Triflps2, Tnf-/-, and Ifnar1-/- mice. We also examined L5 ligation in Tlr4-/- female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferroni post hoc test was used.ResultsIn WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in female Tlr4-/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNβ, released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia.ConclusionsThese observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice

Comparison of gaze behaviour of trainee and experienced surgeons during laparoscopic gastric bypass.

BACKGROUND: Eye tracking presents a novel tool that could be used to profile skill levels in surgery objectively. The primary aim of this study was to identify differences in gaze behaviour between expert and junior surgeons performing a laparoscopic Roux-en-Y gastric bypass (LRYGB) for obesity. METHODS: This prospective observational study used a lightweight eye-tracking apparatus to determine the difference in gaze behaviours between expert (more than 75 procedures) and junior (75 or fewer procedures) surgeons at defined stages of LRYGB. Primary endpoints were normalized dwell time and fixation frequency. Secondary endpoints were blink rate, maximum pupil size and rate of pupil change. RESULTS: A total of 20 procedures (12 junior, 8 expert) were analysed. Compared with juniors, experts showed a prolonged dwell time on the screen during angle of His dissection (median (range) 91·20 (83·40-94·40) versus 68·95 (59·80-87·60) per cent; P = 0·001), formation of the retrogastric tunnel (91·50 (85·80-95·50) versus 73·60 (34·60-90·50) per cent; P = 0·001) and gastric pouch formation (86·95 (83·60-90·20) versus 67·60 (37·10-80·00) per cent P < 0·001). Juniors had a greater blink frequency throughout all recorded segments (P < 0·010) and had a larger maximum pupil size during all recorded operative segments (P < 0·010). Rate of pupil change was greater in juniors in all analysed segments (P < 0·010). CONCLUSION: These results suggest that experts display more focused attention on significant stimuli, alongside experiencing a reduced mental workload and having increased concentration. This has the potential for future use in validation of surgical skill in high-stakes assessment

Nucleotide-Oligomerization-Domain-2 Affects Commensal Gut Microbiota Composition and Intracerebral Immunopathology in Acute Toxoplasma gondii Induced Murine Ileitis

Background Within one week following peroral high dose infection with Toxoplasma (T.) gondii, susceptible mice develop non-selflimiting acute ileitis due to an underlying Th1-type immunopathology. The role of the innate immune receptor nucleotide-oligomerization-domain-2 (NOD2) in mediating potential extra-intestinal inflammatory sequelae including the brain, however, has not been investigated so far. Methodology/Principal Findings Following peroral infection with 100 cysts of T. gondii strain ME49, NOD2-/- mice displayed more severe ileitis and higher small intestinal parasitic loads as compared to wildtype (WT) mice. However, systemic (i.e. splenic) levels of pro-inflammatory cytokines such as TNF-α and IFN-γ were lower in NOD2-/- mice versus WT controls at day 7 p.i. Given that the immunopathological outcome might be influenced by the intestinal microbiota composition, which is shaped by NOD2, we performed a quantitative survey of main intestinal bacterial groups by 16S rRNA analysis. Interestingly, Bifidobacteria were virtually absent in NOD2-/- but not WT mice, whereas differences in remaining bacterial species were rather subtle. Interestingly, more distinct intestinal inflammation was accompanied by higher bacterial translocation rates to extra- intestinal tissue sites such as liver, spleen, and kidneys in T. gondii infected NOD2-/- mice. Strikingly, intracerebral inflammatory foci could be observed as early as seven days following T. gondii infection irrespective of the genotype of animals, whereas NOD2-/- mice exhibited higher intracerebral parasitic loads, higher F4/80 positive macrophage and microglia numbers as well as higher IFN-γ mRNA expression levels as compared to WT control animals. Conclusion/Significance NOD2 signaling is involved in protection of mice from T. gondii induced acute ileitis. The parasite-induced Th1-type immunopathology at intestinal as well as extra-intestinal sites including the brain is modulated in a NOD2-dependent manner

Maternal Antibiotic-Induced Early Changes in Microbial Colonization Selectively Modulate Colonic Permeability and Inducible Heat Shock Proteins, and Digesta Concentrations of Alkaline Phosphatase and TLR-Stimulants in Swine Offspring

Elevated intake of high energy diets is a risk factor for the development of metabolic diseases and obesity. High fat diets cause alterations in colonic microbiota composition and increase gut permeability to bacterial lipopolysaccharide, and subsequent low-grade chronic inflammation in mice. Chronic inflammatory bowel diseases are increasing worldwide and may involve alterations in microbiota-host dialog. Metabolic disorders appearing in later life are also suspected to reflect changes in early programming. However, how the latter affects the colon remains poorly studied. Here, we hypothesized that various components of colonic physiology, including permeability, ion exchange and protective inducible heat shock proteins (HSP) are influenced in the short- and long-terms by early disturbances in microbial colonization. The hypothesis was tested in a swine model. Offspring were born to control mothers (n = 12) or mothers treated with the antibiotic (ATB) amoxicillin around parturition (n = 11). Offspring were slaughtered between 14 and 42 days of age to study short-term effects. For long-term effects, young adult offspring from the same litters consumed a normal or a palm oil-enriched diet for 4 weeks between 140 and 169 days of age. ATB treatment transiently modified maternal fecal microbiota although the minor differences observed for offspring colonic microbiota were nonsignificant. In the short-term, consistently higher HSP27 and HSP70 levels and transiently increased horseradish peroxidase permeability in ATB offspring colon were observed. Importantly, long-term consequences included reduced colonic horseradish peroxidase permeability, and increased colonic digesta alkaline phosphatase (AP) and TLR2- and TLR4-stimulant concentrations in rectal digesta in adult ATB offspring. Inducible HSP27 and HSP70 did not change. Interactions between early ATB treatment and later diet were noted for paracellular permeability and concentrations of colonic digesta AP. In conclusion, our data suggest that early ATB-induced changes in bacterial colonization modulate important aspects of colonic physiology in the short- and longterms