Bipolar impedance-controlled sealing of the pulmonary artery with SealSafe G3 electric current: determination of bursting pressures in an ex vivo model

Background

In every anatomic lung resection operation, the pulmonary artery itself or its branches must be sealed. This involves either stapling or ligating the vessels. Based on the positive results with the bipolar vessel sealing ≤7 mm in abdominal surgery the present study aimed to evaluate burst pressures of the pulmonary artery after sealing with the sealing instrument SealSafe G3 (Gebrüder Martin & CoKG, Tuttlingen, Germany).

Material and methods

The whole pulmonary artery above the pulmonary valve was exposed up to the periphery of the left lung in freshly removed pig heart–lung blocks. A pressure-measuring cylinder was then implanted in the prepared vessel on the side at the main trunk of the pulmonary artery to determine the pressure in the vessel. After either ligation or bipolar sealing of the pulmonary artery, the pneumatic burst pressure (millimeters of mercury) was determined in a water bath. Three groups (n = 12 for each seal type) with different vessel diameters were examined: group 1: 0–6 mm, group 2: 7–12 mm, and group 3: >12 mm. In all cases, vessel sealing was performed with a MARSEAL 5 instrument (Gebrüder Martin & Co KG, Tuttlingen, Germany) and the SealSafe G3 current. The mean burst pressures of the individual groups (ligature and bipolar sealing) were compared using two-tailed, nonparametric Mann–Whitney U test. Significance was defined as P < 0.05.

Results

The mean burst pressures in group 1 were measured by 340 ± 13.4 mm Hg with ligature and 205 ± 44.4 mm Hg with bipolar sealing (P < 0.001). In group 2, the mean values obtained were 270 ± 28.2 mm Hg for ligature and 162 ± 36.0 mm Hg for bipolar sealing (P < 0.001). In group 3, the mean burst pressures for bipolar sealing were only 52.1 ± 15.1 mm Hg, whereas those for ligated vessels were 253 ± 46.9 mm Hg (P < 0.001). For this size of vessel the burst pressure was also determined after stapling. The mean value in this case was 230 ± 21.8 mm Hg.

Conclusions

In all groups, the mean burst pressures after bipolar sealing were significantly lower than those achieved with ligation, but they were sufficient for a save closure of the pulmonary artery with diameters up to 12 mm.     

Selective hydroxylation of aryl iodides to produce phenols under mild conditions using a supported copper catalyst

Owing to the high activity and low-cost, copper-based catalysts are promising candidates for transforming aromatic halides to yield phenols. In this work, we report the selective hydroxylation of aromatic iodides to produce phenols using an atomically dispersed copper catalyst (Cu–ZnO–ZrO₂) under mild reaction conditions. The reactions were conducted without the use of additional organic ligands, and the protection of an inert atmosphere environment is not required. The catalyst can be easily prepared, scalable, and is very efficient for a wide range of substrates. The catalytic reactions can be carried out with only 1.24 mol% Cu loading, which shows great potential in mass production.

Atomically dispersed Cu catalyst was designed for highly efficient hydroxylation of aryl iodides under mild conditions.     

Biperiden and mepazine effectively inhibit MALT1 activity and tumor growth in pancreatic cancer

MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.     

Theoretical potential for endometrial cancer prevention through primary risk factor modification: Estimates from the EPIC cohort

Endometrial cancer (EC) incidence rates vary ~10-fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low-risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow-up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m²), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m²) and HT use (to all non-HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks.     

Cognitive interviewing to improve women's empowerment questions in surveys: Application to the health and nutrition and intrahousehold relationships modules for the project‐level Women's Empowerment in Agriculture Index

In 2015, the United Nations adopted the Sustainable Development Goals, which include fostering gender equality and women's empowerment and ending hunger and malnutrition. To monitor progress and evaluate programmes that aim to achieve these goals, survey instruments are needed that can accurately assess related indicators. The project‐level Women's Empowerment in Agriculture Index (pro‐WEAI) is being developed to address the need for an instrument that is sensitive to changes in empowerment over the duration of an intervention. The pro‐WEAI includes new modules with previously untested survey questions, including a health and nutrition module (focused on women's agency in this area) and an intrahousehold relationships module. This study uses cognitive interviewing to identify how new survey questions might be misinterpreted and to understand what experiences women are referencing when they respond to these questions. This was undertaken with the goal of informing revision to the modules. The study was conducted in Bangladesh with women from nuclear, extended, and migrant‐sending households and from two regions of the country to identify difficulties with interpretation and response formulation across these groups. Findings revealed that questions were generally understood, but participants occasionally responded to the wrong part of the question, did not understand key phrases, or were uncomfortable with questions. The findings also suggested ways to revise the modules and strengthen the pro‐WEAI. The revised pro‐WEAI health and nutrition and intrahousehold relationships modules will advance the ability to measure changes in these domains and their relationship with the health and nutritional status of women and their children.     

In vivo requirement of TGF-β/GDNF cooperativity in mouse development: focus on the neurotrophic hypothesis

Neurotrophic factors are well-recognized extracellular signaling molecules that regulate neuron development including neurite growth, survival and maturation of neuronal phenotypes in the central and peripheral nervous system. Previous studies have suggested that TGF-β plays a key role in the regulation of neuron survival and death and potentiates the neurotrophic activity of several neurotrophic factors, most strikingly of GDNF. To test the physiological relevance of this finding, TGF-β2/GDNF double mutant (d-ko) mice were generated. Double mutant mice die at birth like single mutants due to kidney agenesis (GDNF−/−) and congential cyanosis (TGF-β2−/−), respectively. To test for the in vivo relevance of TGF-β2/GDNF cooperativity to regulate neuron survival, mesencephalic dopaminergic neurons, lumbar motoneurons, as well as neurons of the lumbar dorsal root ganglion and the superior cervical ganglion were investigated. No loss of mesencephalic dopaminergic neurons was observed in double mutant mice at E18.5. A partial reduction in neuron numbers was observed in lumbar motoneurons, sensory and sympathetic neurons in GDNF single mutants, which was further reduced in TGF-β2/GDNF double mutant mice at E18.5. However, TGF-β2 single mutant mice showed no loss of neurons. These data point towards a cooperative role of TGF-β2 and GDNF with regard to promotion of survival within the peripheral motor and sensory systems investigated.     

Testicular morphology and antispermatogenic effects of 2,4-dichlorophenoxyacetic acid (2,4-D) in male West African Dwarf (WAD) goats

This study investigated the testicular morphology as well as the gonadal and extra-gonadal sperm reserves of West African Dwarf (WAD) goats exposed to graded levels of 2,4-dichlorophenoxyacetic acid (2,4-D). Twenty male WAD goats of five goats per group were used for this study. Goats in groups A, B and C received low [75?mg/kg body weight (BW)], medium (100?mg/kg BW) and high (125?mg/kg BW) dose levels of 2,4-D, respectively. The group D goats served as the control. On day?112, goats in the four groups were sacrificed and the testicular and epididymal sperm reserves were determined. Histopathologic changes in the testis of the 2,4-D-exposed and control goats were also assessed. The mean number of spermatozoa in the testes and the various segments of the epididymides decreased significantly (p?<?0.05) in all the treatment groups relative to the control. Combined testicular sperm reserve per millilitre for the treatment groups (group A—19.61?±?2.63?×?10⁸, group B—12.02?±?1.02?×?10⁸ and group C—9.95?±?0.97?×?10⁸) reduced significantly (p?<?0.05) relative to the mean value (23.52?±?4.43?×?10⁸) of the control—group D. The total epididymal sperm reserve per millilitre in the treatment groups (group A—24.25?±?4.19?×?10⁸, group B—17.18?±?2.57?×?10⁸ and group C—17.88?±?2.89?×?10⁸) was also found to be significantly (p?<?0.05) lower than the mean value (40.85?±?11.24?×?10⁸) for the control—group D. This reduction in the testicular and epididymal sperm counts of the 2,4-D-exposed WAD goats in this study suggest disruption in spermatogenic activity, which may lead to low productivity. Variable degrees of circulatory disturbances were observed in the testis sections of 2,4-D-exposed goats.     

Microsatellite instability in pediatric and adult high-grade gliomas

About 15% of sporadic gastrointestinal and endometrial tumors show the microsatellite instability (MSI) phenotype because of loss of DNA mismatch repair (MMR) function. The incidence of MSI in tumors of the central nervous system still remains controversial. Previous studies reported a particular high frequency of MSI (approximately 25%) in young patients suffering from high-grade gliomas. Based on these data and the fact that in different tumor entities MMR deficiency defines a subgroup of tumors with distinct pathogenesis and particular clinicopathological features that may have impact on prognosis and therapy, we screened 624 gliomas from 71 young and 553 adult patients for MMR deficiency by MSI analysis using three highly sensitive diagnostic markers. Alterations of MMR protein expression was examined by immunohistochemistry. A malignant glioma from an adult patient displayed MSI and concomitant loss of nuclear MSH2 and MSH6 protein expression (0.16%; 1/619). No evidence for MSI or loss of MMR protein expression was observed in 71 gliomas from young patients (0%; 0/71) including 41 high-grade astrocytic tumors. Overall, we observed a much lower incidence of MSI among high-grade pediatric gliomas than initially reported and suggest that MMR deficiency does not play a major role in the pathogenesis of glial neoplasms.     

Mechanically functional amyloid fibrils in the adhesive of a marine invertebrate as revealed by Raman spectroscopy and atomic force microscopy

Amyloid fibrils are primarily known in a pathogenic context for their association with a wide range of debilitating human diseases. Here we show a marine invertebrate (Entobdella soleae) utilizes functional amyloid fibrils comparable to those of a unicellular prokaryote (Escherichia coli). Thioflavin-T binding and Raman spectroscopy provided evidence for the presence of amyloid in the adhesive of Entobdella soleae. We elucidated that for these two very different organisms, amyloid fibrils provide adhesive and cohesive strength to their natural adhesives. Comparing the nanoscale mechanical responses of these fibrils with those of pathogenic amyloid by atomic force microscopy revealed that the molecular level origin of the cohesive strength was associated with the generic intermolecular β-sheet structure of amyloid fibrils. Functional adhesive residues were found only in the case of the functional amyloid. Atomic force microscopy provided a useful means to characterize the internal structural forces within individual amyloid fibrils and how these relate to the mechanical performance of both functional and pathogenic amyloid. The mechanistic link of amyloid-based cohesive and adhesive strength could be widespread amongst natural adhesives, irrespective of environment, providing a new strategy for biomimicry and a new source of materials for understanding the formation and stability of amyloid fibrils more generally.