Mesothelial cells in tissue repair and fibrosis

Mesothelial cells are fundamental to the maintenance of serosal integrity and homeostasis and play a critical role in normal serosal repair following injury. However, when normal repair mechanisms breakdown, mesothelial cells take on a profibrotic role, secreting inflammatory, and profibrotic mediators, differentiating and migrating into the injured tissues where they contribute to fibrogenesis. The development of new molecular and cell tracking techniques has made it possible to examine the origin of fibrotic cells within damaged tissues and to elucidate the roles they play in inflammation and fibrosis. In addition to secreting proinflammatory mediators and contributing to both coagulation and fibrinolysis, mesothelial cells undergo mesothelial-to-mesenchymal transition, a process analogous to epithelial-to-mesenchymal transition, and become fibrogenic cells. Fibrogenic mesothelial cells have now been identified in tissues where they have not previously been thought to occur, such as within the parenchyma of the fibrotic lung. These findings show a direct role for mesothelial cells in fibrogenesis and open therapeutic strategies to prevent or reverse the fibrotic process

Natural variation in gestational cortisol is associated with patterns of growth in marmoset monkeys (Callithrix geoffroyi)

High levels of prenatal cortisol have been previously reported to retard fetal growth. Although cortisol plays a pivotal role in prenatal maturation, heightened exposure to cortisol can result in lower body weights at birth, which have been shown to be associated with adult diseases like hypertension and cardiovascular disease. This study examines the relationship between natural variation in gestational cortisol and fetal and postnatal growth in marmoset monkeys. Urinary samples obtained during the mother’s gestation were analyzed for cortisol. Marmoset body mass index (BMI) was measured from birth through 540 days in 30- or 60-day intervals. Multi-level modeling was used to test if marmoset growth over time was predicted by changes in gestational cortisol controlling for time, sex, litter, and litter size. The results show that offspring exposed to intra-uterine environments with elevated levels of cortisol had lower linear BMI rates of change shortly after birth than did offspring exposed to lower levels of cortisol, but exhibited a higher curvilinear growth rate during adolescence. Average daily change in gestational cortisol during the first trimester had a stronger relationship with postnatal growth than change during the third trimester. Higher exposure to cortisol during gestation does alter developmental trajectories, however there appears to be a catch-up period during later post-natal growth. These observations contribute to a larger discussion about the relationship of maternal glucocorticoids on offspring development and the possibility of an earlier vulnerable developmental window

A practical guide and perspectives on the use of experimental pain modalities with children and adolescents

Use of experimental pain is vital for addressing research questions that would otherwise be impossible to examine in the real world. Experimental induction of pain in children is highly scrutinized given the potential for harm and lack of direct benefit to a vulnerable population. However, its use has critically advanced our understanding of the mechanisms, assessment and treatment of pain in both healthy and chronically ill children. This article introduces various experimental pain modalities, including the cold pressor task, the water load symptom provocation test, thermal pain, pressure pain and conditioned pain modulation, and discusses their application for use with children and adolescents. It addresses practical implementation and ethical issues, as well as the advantages and disadvantages offered by each task. The incredible potential for future research is discussed given the array of experimental pain modalities now available to pediatric researchers

A Single-Center Comparison of Extended and Restricted THROMBOPROPHYLAXIS with LMWH after Metabolic Surgery

IntroductionMorbid obesity is an important risk factor for developing a venous thromboembolic events (VTE) after surgery. Fast-track protocols in metabolic surgery can lower the risk of VTE in the postoperative period by reducing the immobilization period. Administration of thromboprophylaxis can be a burden for patients. This study aims to compare extended to restricted thromboprophylaxis with low molecular weight heparin (LMWH) for patients undergoing metabolic surgery.MethodsIn this single center retrospective cohort study, data was collected from patients undergoing a primary Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between 2014 and 2018. Patients operated in 2014-2017 received thromboprophylaxis for two weeks. In 2018, patients only received thromboprophylaxis during hospital admission. Patients already using anticoagulants were analyzed as a separate subgroup. The primary outcome measure was the rate of clinically significant VTEs within three months. Secondary outcome measures were postoperative hemorrhage and reoperations for hemorrhage.Results3666 Patients underwent a primary RYGB or SG following the fast-track protocol. In total, two patients in the 2014-2017 cohort were diagnosed with VTE versus zero patients in the 2018 cohort. In the historic group, 34/2599 (1.3%) hemorrhages occurred and in the recent cohort 8/720 (1.1%). Postoperative hemorrhage rates did not differ between the two cohorts (multivariable analysis, p=0.475). In the subgroup of patients using anticoagulants, 21/347(6.1%) patients developed a postoperative hemorrhage. Anticoagulant use was a significant predictor of postoperative hemorrhage (

Low-pressure pneumoperitoneum with deep neuromuscular blockade in metabolic surgery to reduce postoperative pain:a randomized pilot trial

Background For metabolic laparoscopic surgery, higher pressures up to 20 mmHg are often used to create a surgical field of sufficient quality. This randomized pilot study aimed to determine the feasibility, safety and tolerability of low intraabdominal pressure (IAP) and deep neuromuscular blockade (NMB) to reduce postoperative pain. Methods In a teaching hospital in the Netherlands, 62 patients eligible for a laparoscopic Roux-en-Y gastric bypass (LRYGB) were randomized into one of four groups in a 2 x 2 factorial design: deep/moderate NMB and standard (20 mmHg)/low IAP (12 mmHg). Patient and surgical team were blinded. Primary outcome measure was the surgical field quality, scored on the Leiden-Surgical Rating Scale (L-SRS). Secondary outcome measures were (serious) adverse events, duration of surgery and postoperative pain. Results 62 patients were included. L-SRS was good or perfect in all patients that were operated under standard IAP with deep or moderate NMB. In 40% of patients with low IAP and deep NMB, an increase in IAP was needed to improve surgical overview. In patients with low IAP and moderate NMB, IAP was increased to improve surgical overview in 40%, and in 75% of these cases a deep NMB was requested to further improve the surgical overview. Median duration of surgery was 38 min (IQR34-40 min) in the group with standard IAP and moderate NMB and 52 min (IQR46-55 min) in the group with low IAP and deep NMB. Conclusions The combination of moderate NMB and low IAP can create insufficient surgical overview. Larger trials are needed to corroborate the findings of this study. Trial registration: Dutch Trial Register: Trial NL7050, registered 28 May 2018.

An evaluation of a multi-component adult weight management on referral intervention in a community setting

BACKGROUND: National Institute for Health and Care Excellence (NICE) guidance on adult weight management recommends interventions are multi-component. We aimed to assess the implementation and health benefits of a primary care referral to an adult multi-component weight management intervention in a community setting. The intervention was offered through Primary care in National Health Service (NHS) South Gloucestershire, UK, from Oct 2008 to Nov 2010, in partnership with statutory, community and commercial providers. The scheme offered 12 weeks’ community based concurrent support of dietary (Weight Watchers, WW), physical activity (Exercise on Prescription, EOP) and behavioural change (motivational interviewing) components to obese adults. Funding was available for 600 places. RESULTS: Five hundred and fifty nine participants engaged with the intervention, mean age 48 years, 88 % female. Mean weight loss for all engagers was 3.7 kg (95 % confidence interval 3.4, 4.1). Participants completing the intervention achieved the largest weight reduction (mean loss 5.9 kg; 5.3, 6.6). Achievement of 5 % weight loss was higher in completers (58 %; 50, 65) compared to non-completers (19 %; 12, 26) and people who only participated in one commercial component of the intervention (either WW or EOP; 19 %; 13, 24). CONCLUSION: A multi-component weight management programme may be beneficial for weight loss, but a randomized controlled trial is needed to establish effectiveness and to evaluate cost

Putative markers for the detection of breast carcinoma cells in blood.

The aim of this study was to investigate certain genes for their suitability as molecular markers for detection of breast carcinoma cells using the reverse transcriptase-polymerase chain reaction (RT-PCR). RNA was prepared from MCF-7 breast carcinoma cells and peripheral blood leucocytes of healthy female volunteers. This RNA was screened for mRNA of MUC1, cytokeratin 19 (CK19) and CD44 (exons 8-11) by RT-PCR and the results validated by Southern blots. Variable degrees of expression of MUC1 and CD44 (exons 8-11) were detected in normal peripheral blood, rendering these genes non-specific for epithelial cells and therefore unsuitable for use as markers to detect breast carcinoma cells. Although CK19 mRNA was apparently specific, it was deemed unsuitable for use as a marker of breast cancer cells in light of its limited sensitivity. Furthermore, an attempt at using nested primers to increase sensitivity resulted in CK19 mRNA being detected after two amplification rounds in blood from healthy volunteers