Search

During early neural development, changes in signalling inform the expression of transcription factors that in turn instruct changes in cell identity. At the same time, switches in adhesion molecule expression result in cellular rearrangements that define the morphology of the emerging neural tube. It is becoming increasingly clear that these two processes influence each other; adhesion molecules do not simply operate downstream of or in parallel with changes in cell identity but rather actively feed into cell fate decisions. Why are differentiation and adhesion so tightly linked? It is now over 60 years since Conrad Waddington noted the remarkable "Constancy of the Wild Type" (Waddington in Nature 183: 1654-1655, 1959) yet we still do not fully understand the mechanisms that make development so reproducible. Conversely, we do not understand why directed differentiation of cells in a dish is sometimes unpredictable and difficult to control. It has long been suggested that cells make decisions as 'local cooperatives' rather than as individuals (Gurdon in Nature 336: 772-774, 1988; Lander in Cell 144: 955-969, 2011). Given that the cadherin family of adhesion molecules can simultaneously influence morphogenesis and signalling, it is tempting to speculate that they may help coordinate cell fate decisions between neighbouring cells in the embryo to ensure fidelity of patterning, and that the uncoupling of these processes in a culture dish might underlie some of the problems with controlling cell fate decisions ex-vivo. Here we review the expression and function of cadherins during early neural development and discuss how and why they might modulate signalling and differentiation as neural tissues are formed.

Background: Knowledge about mineral bone disorder (MBD) management in non-dialysis chronic kidney disease (ND-CKD) patients is scarce, although essential to identifying areas for therapeutic improvement., Methods: We prospectively evaluated current management of CKD-MBD in two visits, performed 6 months apart, in 727 prevalent ND-CKD stage 3b-5 patients from 19 nephrology clinics. Therapeutic inertia was defined as lack of treatment despite hyperphosphatemia and/or hypocalcemia, and/or hyperparathyroidism. The primary endpoint was the prevalence of achieved target for CKD-MBD parameters and related treatments (phosphate binders, vitamin D and calcium supplements). The secondary endpoint was the assessment of prevalence and clinical correlates of therapeutic inertia., Results: Over 65 % of patients did not reach parathormone (PTH) targets, while 15 and 19 % did not reach phosphate and calcium targets, respectively. The proportion of untreated patients decreased from stage 3b to 5 (at baseline, from 60 to 16 %, respectively). From baseline to the 6-month visit, the achievement of targets remained stable. Low protein diet was prescribed in 26 % of patients, phosphate binders in 17.3 % (calcium-based binders 15.5 %, aluminium binders 1.8 %), and vitamin D in 50.5 %. The overall prevalence of therapeutic inertia at the 6-month visit was 34.0 % (for hyperphosphatemia, 54.3 %). Compared to CKD stage 3, the likelihood of therapeutic inertia was 40 and 68 % lower at stage 4 and 5, respectively., Conclusions: PTH, calcium and phosphate targets were not reached in a significant proportion of patients. One-third of patients with at least one MBD parameter not-at-target remained untreated. Therapeutic inertia regarding CKD-MBD treatment may be a major barrier to optimizing the prevention and cure of CKD-MBD.

TAPSE measurement during echocardiography is a well known measure of right heart systo-diastolic function. Low TAPSE means reduced cranio-caudal excursion of tricuspidal annulus, sign of both reduced ejection fraction and reduced distensibility of right ventricle. It is a good prognostic index for cardiac mortality risk in CHF patients, adding significant prognostic information to NYHA stadiation. Nephrologists do not always fully aware of right ventricular function in their patients affected by chronic renal failure (CRF), even if this datum is probably crucial in vascular access policy. Our study was designed to study right ventricle function and TAPSE on 202 patients affected by moderate chronic renal failure, free from overt pulmonary hypertension. TAPSE, PAPs, right chambers diameters, classical Framingham factors, estimated glomerular filtration rate were recorded. TAPSE was reduced (<23 mm) in 43% of patients enrolled, while dilated right chambers were present in 24%. PAPs exceeded 30 mmHg in 29% of patients. Echocardiographic signs of left ventricular hypertrophy were found in 36% of patients. The ejection fraction was normal in all patients. Statistical analysis showed a significant indirect correlation between TAPSE and PAPs and between TAPSE and tele-diastolic diameters and volumes of the right ventricle, while a direct correlation was observed between TAPSE and Framingham score. TAPSE showed a bimodal distribution, with a subpopulation "low TAPSE - high PAPs", next to a population characterized by normal values ??for both parameters. A reduction in compliance and systolic function of the right heart chambers is quite early and frequent in course of CKD, a fact that the nephrologist should take in due consideration, managing blood volume or planning vascular access for hemodialysis.

Background: Many patients with established hypertension have poorly controlled blood pressure (BP). We studied demographic and clinical characteristics related to hypertension and analyzed the relationships between BP control and comorbidity., Methods: This study was based on 414 consecutive hypertensive out-patients referred to our nephrology clinic. We recorded systolic and diastolic BP, age, gender, body mass index, total cholesterol, family history of hypertension, glomerular filtration rate (GFR), 24-hr proteinuria, diabetes, coronary artery disease, smoking habits and antihypertensive drug treatment. BP control was considered optimal if BP was < 130/80 mmHg in patients with diabetes or chronic kidney disease (CKD), if BP was < 125/75 mmHg in CKD with proteinuria > 1 g/24 hr and if BP was < 140/90 mmHg in patients with no comorbidity. Multivariate logistic regression analysis was used to investigate the association between BP control and predictors., Results: Only 26.6% of patients had adequately controlled BP. Eighty-five percent of patients aged > 65 yrs had uncontrolled systolic hypertension. Univariate analysis showed a significant association between poor BP control and age >65 yrs, family history of hypertension, diabetes, CKD with or without proteinuria > 1 g/24 hr and total cholesterol > 220 mg/dL. Multivariate logistic regression showed that age > 65 yrs, diabetes and CKD with or without proteinuria > 1 g/24 hr were significantly and independently associated with poor BP control., Conclusions: Inadequate hypertension control is a common cause for referral to our out-patient nephrology clinic. Our data confirm that elderly patients, diabetic patients and nephropathic patients are difficult to treat; and therefore, deserve the highest quality clinical attention.

Background: The risks connected with dialysis fluid contamination are well established. Epidemiological studies have demonstrated just how difficult it is to obtain permanently satisfactory quality standards. Therefore, dialysis centers must have effective and regular quality control programs, particularly with the growing and widespread use of online convective dialysis treatments. Considering this, we conducted a national survey of water treatment systems and monitoring in Italian dialysis centers., Methods: Two independent questionnaires were prepared and distributed in 1999 and 2001. The questions were designed to acquire information on structural and procedural elements. Responses to similar questions from both questionnaires were analyzed together., Results: Responses to questionnaires were received from 148 centers (17% of dialysis centers in Italy). In accordance with the European Best Practice Guidelines (EBPG) published recently concerning dialysis fluid purity, in the majority of centers (97%) the water treatment system consisted of at least pre-treatment and reverse osmosis (RO) modules. However, only one stage RO module was implemented (71%), there was a water storage tank (65%) and water pipe distribution loop was made of sanitary polyvinyl chloride (85%). Analysis of procedural elements--the timing and type of disinfection procedures used for the waterline system and monitors, the timing and type of water treatment quality control procedures--revealed a striking variability among centers in terms of the types and frequency of checks performed., Conclusions: Taking into account the EBPG, this survey revealed both bright and dark spots, calling for a national initiative aimed at defining a standard periodicity of loop disinfection, points in the water pipe line to be tested, and the frequency and type of tests.