The role of gentle touch in perinatal osteopathic manual therapy.

Osteopathic medicine is a system of manual diagnosis and treatment. While there is growing evidence that osteopathy is effective in a range of clinical conditions, the underlying biological basis of its therapeutic effects remain largely unknown. Given that the sense of touch plays a critical role in osteopathy, in this perspective article, with a particular focus on perinatal care, we explore the potential mechanisms by which stimulation of the skin senses can exert beneficial physiological and psychological effects, aiding growth and development. We propose that a class of low threshold mechanosensitive c-fibre, named c-tactile afferents, which respond optimally to gentle, slow moving touch are likely to play a direct and significant role in the efficacy of manual therapies. A greater understanding of the impact the type and quality of touch plays in therapeutic tactile interventions and in particular the neuroscience underpinning these effects will aid the development of more targeted, population specific interventions

The implications of three major new trials for the effect of water, sanitation and hygiene on childhood diarrhea and stunting: a consensus statement

BACKGROUND: Three large new trials of unprecedented scale and cost, which included novel factorial designs, have found no effect of basic water, sanitation and hygiene (WASH) interventions on childhood stunting, and only mixed effects on childhood diarrhea. Arriving at the inception of the United Nations' Sustainable Development Goals, and the bold new target of safely managed water, sanitation and hygiene for all by 2030, these results warrant the attention of researchers, policy-makers and practitioners. MAIN BODY: Here we report the conclusions of an expert meeting convened by the World Health Organization and the Bill and Melinda Gates Foundation to discuss these findings, and present five key consensus messages as a basis for wider discussion and debate in the WASH and nutrition sectors. We judge these trials to have high internal validity, constituting good evidence that these specific interventions had no effect on childhood linear growth, and mixed effects on childhood diarrhea. These results suggest that, in settings such as these, more comprehensive or ambitious WASH interventions may be needed to achieve a major impact on child health. CONCLUSION: These results are important because such basic interventions are often deployed in low-income rural settings with the expectation of improving child health, although this is rarely the sole justification. Our view is that these three new trials do not show that WASH in general cannot influence child linear growth, but they do demonstrate that these specific interventions had no influence in settings where stunting remains an important public health challenge. We support a call for transformative WASH, in so much as it encapsulates the guiding principle that - in any context - a comprehensive package of WASH interventions is needed that is tailored to address the local exposure landscape and enteric disease burden

FGFR1 Expression and Role in Migration in Low and High Grade Pediatric Gliomas

The heterogeneous and invasive nature of pediatric gliomas poses significant treatment challenges, highlighting the importance of identifying novel chemotherapeutic targets. Recently, recurrent Fibroblast growth factor receptor 1 (FGFR1) mutations in pediatric gliomas have been reported. Here, we explored the clinical relevance of FGFR1 expression, cell migration in low and high grade pediatric gliomas and the role of FGFR1 in cell migration/invasion as a potential chemotherapeutic target. A high density tissue microarray (TMA) was used to investigate associations between FGFR1 and activated phosphorylated FGFR1 (pFGFR1) expression and various clinicopathologic parameters. Expression of FGFR1 and pFGFR1 were measured by immunofluorescence and by immunohistochemistry (IHC) in 3D spheroids in five rare patient-derived pediatric low-grade glioma (pLGG) and two established high-grade glioma (pHGG) cell lines. Two-dimensional (2D) and three-dimensional (3D) migration assays were performed for migration and inhibitor studies with three FGFR1 inhibitors. High FGFR1 expression was associated with age, malignancy, tumor location and tumor grade among astrocytomas. Membranous pFGFR1 was associated with malignancy and tumor grade. All glioma cell lines exhibited varying levels of FGFR1 and pFGFR1 expression and migratory phenotypes. There were significant anti-migratory effects on the pHGG cell lines with inhibitor treatment and anti-migratory or pro-migratory responses to FGFR1 inhibition in the pLGGs. Our findings support further research to target FGFR1 signaling in pediatric gliomas

A novel workflow for three-dimensional analysis of tumour cell migration

The limitations of two-dimensional analysis in three-dimensional (3D) cellular imaging impair the accuracy of research findings in biological studies. Here, we report a novel 3D approach to acquisition, analysis and interpretation of tumour spheroid images. Our research interest in mesenchymal–amoeboid transition led to the development of a workflow incorporating the generation and analysis of 3D data with instant structured illumination microscopy and a new ImageJ plugin

Assessing the Effects of the Transition from Multiple Daily Insulin Injections (MDI) to Continuous Subcutaneous Insulin Infusion in the Intensive Treatment of Type 1 Diabetes Mellitus

Introduction: Intensive insulin therapy is currently the main treatment in type I diabetes mellitus (DM) which includes multiple daily insulin injections (MDI) and continuous subcutaneous insulin infusion (CSII). The latter has become the preferred therapeutic mode, since it better mimics the physiological pancreatic action, althought there is limited evidence that supports its superiority to MDI. The aim of our study was to assess the effects of the transition from MDI to CSII in the intensive treatment of type 1 DM. Material and Methods: A retrospective longitudinal study was perfonned in MDI patients that transited to CSII between 2006 and 2014. Data were collected regarding to weight, HbA1c, plasma glucose, lipid profile, creatinine, weekly frequency of episodes of hypoglycemia and hyperglycemia and presence of microvascular complications. The effects of the transition to CSII were also compared according to the following subgroups: pre-CSII HbA1c (7.0%); age ( 35 years); gender (male versus female); BMI (25 kg/m2); duration of illness ( 15 years); total daily dose (TDD) of insulin ( 45 units of insulin); ISF ( 40) and microvascular complications (presence versus absence). Results: The sample included 85 patients, mean age 38 +/- 11 years, 50 (58.8%) female, with duration of the disease 21 +/- 9 years. There was a significant reduction in the frequency of hypo and hyperglycemia events after transition to CSII (3.0 +/- 5.0 vs 2 +/- 2.2 per week, p= 0.001 and 5.5 +/- 6.1 vs 2.5 +/- 2.6 per week, p = 0.05, respectively). We also observed a greater glycemic benefit in the subgroups of patients with poorer metabolic control (HbA1c > 7%) compared to those with HbA1c s <= 7% (Delta HbA1c =-0.55% vs 0.20%, respectively, p < 0.05), for the first 6 months after CSII, being additionally reported a significant increase in HDL-C levels (2.81 +/- 10.34 mg/dL, p = 0.039). Conclusion: In this study, CSII therapy was shown to be more effective compared to MDI in patients with poorer metabolic control, being also noted a significant reduction of weekly frequency of hypo and hyperglycemia events. Notwithstanding the encouraging results linked with CSII, in the future, longer longitudinal studies will be mandatory in order to assess the real relative effectiveness of CSII in the treatment of type 1 DM

Drug Resistance in Glioma Cells Induced by a Mesenchymal–Amoeboid Migratory Switch

Cancer cell invasion is a precondition for tumour metastasis and represents one of the most devastating characteristics of cancer. The development of drugs targeting cell migration, known as migrastatics, may improve the treatment of highly invasive tumours such as glioblastoma (GBM). In this study, investigations into the role of the cell adhesion protein Cellular communication network factor 1 (CCN1, also known as CYR61) in GBM cell migration uncovered a drug resistance mechanism adopted by cells when treated with the small molecule inhibitor CCG-1423. This inhibitor binds to importin α/β inhibiting the nuclear translocation of the transcriptional co-activator MKL1, thus preventing downstream effects including migration. Despite this reported role as an inhibitor of cell migration, we found that CCG-1423 treatment did not inhibit GBM cell migration. However, we could observe cells now migrating by mesenchymal–amoeboid transition (MAT). Furthermore, we present evidence that CCN1 plays a critical role in the progression of GBM with increased expression in higher-grade tumours and matched blood samples. These findings support a potential role for CCN1 as a biomarker for the monitoring and potentially early prediction of GBM recurrence, therefore as such could help to improve treatment of and increase survival rates of this devastating disease