Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism

Liver and lung metastases are the predominant cause of colorectal cancer (CRC)-related mortality. Recent research has indicated that CXCR3/chemokines interactions that orchestrate haematopoetic cell movement are implicated in the metastatic process of malignant tumours, including that of CRC cells to lymph nodes. To date, however, the contribution of CXCR3 to liver and lung metastasis in CRC has not been addressed. To determine whether CXCR3 receptors regulate malignancy-related properties of CRC cells, we have used CXCR3-expressing CRC cell lines of human (HT29 cells) and murine (C26 cells) origins that enable the development of liver and lung metastases when injected into immunodeficient and immunocompetent mice, respectively, and assessed the effect of CXCR3 blockade using AMG487, a small molecular weight antagonist. In vitro, activation of CXCR3 on human and mouse CRC cells by its cognate ligands induced migratory and growth responses, both activities being abrogated by AMG487. In vivo, systemic CXCR3 antagonism by preventive or curative treatments with AMG487 markedly inhibited the implantation and the growth of human and mouse CRC cells within lung without affecting that in the liver. In addition, we measured increased levels of CXCR3 and ligands expression within lung nodules compared with liver tumours. Altogether, our findings indicate that activation of CXCR3 receptors by its cognate ligands facilitates the implantation and the progression of CRC cells within lung tissues and that inhibition of this axis decreases pulmonary metastasis of CRC in two murine tumour models

ELECtric Tibial nerve stimulation to Reduce Incontinence in Care homes: protocol for the ELECTRIC randomised trial

Background Urinary incontinence (UI) is highly prevalent in nursing and residential care homes (CH) and profoundly impacts on residents’ dignity and quality of life. Care homes predominantly use absorbent pads to contain UI rather than actively treat the condition. Transcutaneous posterior tibial nerve stimulation (TPTNS) is a non-invasive, safe, low-cost intervention with demonstrated effectiveness for reducing UI in adults. However, the effectiveness of TPTNS to treat UI in older adults living in care homes is not known. The ELECTRIC Trial aims to establish if a programme of TPTNS is a clinically effective treatment for UI in care home residents and investigate the associated costs and consequences. Methods This is a pragmatic, multicentre, placebo controlled randomised parallel group trial comparing effectiveness of TPTNS (target n=250) with sham stimulation (target n=250) in reducing volume of UI in CH residents. CH residents (men and women) with self- or staff- reported UI of more than once per week are eligible to take part, including those with cognitive impairment. Outcomes will be measured at 6, 12 and 18 weeks post randomisation using the following measures: 24-hour pad weight tests (PWT), post void residual urine (bladder scans), Patient Perception of Bladder Condition (PPBC), Minnesota Toileting Skills Questionnaire (MTSQ) and Dementia Quality of Life (DEMQOL). Economic evaluation based on a bespoke Resource Use Questionnaire will assess the costs of providing a programme of TPTNS. A concurrent process evaluation will investigate fidelity to the intervention and influencing factors and qualitative interviews will explore the experiences of TPTNS from the perspective of CH residents, family members, CH staff and managers. Discussion TPTNS is a non-invasive intervention that has demonstrated effectiveness in reducing UI in adults. The ELECTRIC Trial will involve CH staff delivering TPTNS to residents and establish whether TPTNS is more effective than sham stimulation for reducing the volume of UI in CH residents. Should TPTNS be shown to be an effective and acceptable treatment for UI in older adults in CHs, it will provide a safe, low-cost and dignified alternative to the current standard approach of containment and medication. Trial registration Clinical Trials.gov. NCT03248362. Registered on 14/08/2017. https://clinicaltrials.gov/ ISRCTN, ISRCTN 98415244. Registered on 25/04/2018. https://www.isrctn.com

Water beetles (Coleoptera) associated with Afrotemperate Forest patches in the Garden Route National Park, South Africa

Southern Afrotemperate Forest is concentrated in the southern Cape region of South Africa and whilst it is relatively well known botanically, the fauna, specifically the aquatic invertebrate fauna, is poorly documented. The majority of remaining intact forest habitat is contained within the Garden Route National Park (GRNP), which straddles the provincial boundary between the Western and Eastern Cape. This study undertakes a survey of the water beetle fauna inhabiting the GRNP. The aquatic ecosystems within temperate forests of the region are poorly researched from an ecological and biodiversity perspective, despite being known to harbour endemic invertebrate elements. We collected water beetles and in situ physico-chemical data from a total of 31 waterbodies across the park over two seasons (summer and late winter) in 2017. The waterbodies sampled were mostly small freshwater perennial streams and isolated forest ponds. A total of 61 beetle taxa was recorded (29 Adephaga, 32 Polyphaga) from these waterbodies. The water beetle fauna of these forests appears to be diverse and contains many species endemic to the fynbos-dominated Cape Floristic Region, but very few of the species appear to be forest specialists. This is in contrast to the fynbos heathland habitat of the region, which harbours a high number of water beetle species endemic to this habitat, often with Gondwanan affinity. Our study is the first to document the water beetles of Afrotemperate Forests in the southern Cape region and provides an important baseline for future work on such habitats in the region and in other parts of southern Africa

Pelvic Floor Muscle Training in the Treatment of Lower Urinary Tract Dysfunction in women with Multiple Sclerosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Aims: Evaluate the role of Pelvic Floor Muscle Training (PFMT) on the treatment of Lower Urinary Tract Dysfunction (LUTD) in Multiple Sclerosis (MS) patients. Methods: In this randomized controlled trial, twenty seven female patients with a diagnosis of MS and LUTD complaints were randomized, in two groups: Treatment group (GI) (N = 13) and Sham group (GII) (N = 14). Evaluation included urodynamic study, 24-hr Pad testing, three day voiding diary and pelvic floor evaluation according to PERFECT scheme. Intervention was performed twice a week for 12 weeks in both groups. GI intervention consisted of PFMT with assistance of a vaginal perineometer. GII received a sham treatment consisted on the introduction of a perineometer inside the vagina with no contraction required. Results: At the end of the treatment GI was complaining less about storage and voiding symptoms than GII. Furthermore, differences found between groups were: reduction of pad weight (P = 0.00) (Mean: 87,51 grams initial and 6,03 grams final in GI. 69,46 grams initial and 75,88 grams final in GII), number of pads (P = 0.01) (Mean: 3,61 initial and 2,15 final in GI. 3,42 initial and 3,28 final in GII) and nocturia events (P < 0.00) (Mean: 2,38 initial and 0,46 final in GI. 2,55 initial and 2,47 final in GII) and improvements of muscle power (P = 0.00), endurance (P < 0.00), resistance (P < 0.00) and fast contractions (P < 0.00), domains of PERFECT scheme. Conclusion: PFMT is an effective approach to treat LUTD in female with MS. Neurourol. Urodyn. 29:1410-1413, 2010. (C) 2010 Wiley-Liss, Inc.29814101413Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [07/57401-6

Effect of sampling time on urinary electrolytes following oral furosemide administration in dogs with myxomatous mitral valve disease

Introduction/Objectives Urine chemistry has received growing attention to estimate the diuretic response in dogs with cardiac disease. The aim of the study was to evaluate the impact of time elapsed between the oral furosemide administration and sample collection on urine chemistry in dogs with myxomatous mitral valve disease (MMVD) receiving diuretic therapy in American College of Veterinary Internal Medicine (ACVIM) stage C. Materials and methods Seventy-three dogs with MMVD ACVIM stage C and 106 healthy dogs were prospectively included. Dogs with MMVD were divided, based on the time of sampling, in morning group (MMVD-MG) of one to 6 h and an evening group (MMVD-EG) over 6 h from oral furosemide administration. Analogously, healthy dogs sampled between 9 a.m. and 1 p.m. and between 2 and 7 p.m. were divided in a morning group (H-MG) and an evening group (H-EG), respectively. Urine chemistry, including fractional excretion of electrolytes, was evaluated and compared among groups. Results Higher excretion of sodium and chloride and higher urine sodium to urine potassium ratio (uNa+:uK+) were detected in MMVD-MG than MMVD-EG (p = 0.021, p = 0.038, and p = 0.016, respectively). Natriuresis, chloriuresis, and uNa+:uK+ were higher in MMVD-MG than H-MG, while no differences were found in the comparison between H-MG and H-EG and between MMVD-EG and H-EG. Conclusions Urinary electrolyte excretion is significantly increased within 6 h from furosemide administration in MMVD ACVIM stage C dogs. Time of sampling from furosemide administration significantly affects urine chemistry in MMVD dogs and should be considered in clinical practice and the research field