The burden of hypertension and kidney disease in Northeast India: the Institute for Indian Mother and Child noncommunicable diseases project.

Chronic noncommunicable diseases (NCDs) such as hypertension, atherosclerosis, acute myocardial infarction, stroke, diabetes, obesity, and chronic kidney disease are the major cause of death not only in high income, but also in medium and low income countries. Hypertension and diabetes, the most common causes of chronic kidney disease, are particularly common in southeast Asian Countries. Because early intervention can markedly slow the progression of these two killer diseases, assessment of their presence through screening and intervention program is a priority. We summarize here results of the screening activities and the perspectives of a noncommunicable diseases project started in West Bengal, India, in collaboration with the Institute for Indian Mother and Child (IIMC), a nongovernmental voluntary organization committed to promoting child and maternal health. We started investigating hypertension and chronic kidney disease with screen in school-age children and in adults >30 years old. We found a remarkable prevalence of hypertension, even in underweight subjects, in both children and adult populations. A glomerular filtration rate <60 mL/min was found in 4.1% of adult subjects significantly higher than that of 0.8% to 1.4% reported 10 years ago. Increased awareness and intervention projects to identify NCDs and block their progression are necessary in all countries.

Hypertension and kidney function in an adult population of West Bengal, India: role of body weight, waist circumference, proteinuria and rural area living.

AIM: Hypertension (HTN) and chronic kidney disease (CKD) are important emerging problems in low-income countries, with an increasing number of patients dying from their consequences. METHODS: A project for investigating these issues was carried out in West Bengal, India, in 2536 adult subjects. Body mass index (BMI) was classified using traditional and new cut-offs identified by the World Health Organization for Asian populations. HTN was classified according to the Joint National Committee 7 and CKD according to presence of estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m(2) . RESULTS: Normal BMI (Asian reference) was found in 41.5% of subjects, while 33.4% were underweight, 19.3% overweight and 5.8% obese. Prevalence of stage 1 and 2 HTN was 39.4%. Proteinuria (urine dipstick >1+) was present in 7.7% of the sample. In a subsample of 1526 subjects, eGFR of less than 60 mL/min per 1.73 m(2) was found in 4.2%. At multivariate analysis, factors associated with HTN were weight classes (P<0.001), presence of proteinuria (P<0.001) and family history of HTN (P=0.028), while living in rural areas was associated with lower risk for HTN (P=0.003). eGFR was inversely related to BMI (P=0.03), the presence of proteinuria (P<0.001) and HTN (P<0.003), and directly related to living in rural areas (P=0.003). CONCLUSION: High prevalence of HTN was found in subjects with very limited access to health care in West Bengal. HTN was more common in overweight individuals, but also affected normal weight and underweight subjects in a significant part of the tested population. Preventive medicine should be a strong priority in this setting.

[Assessing the quality of life in patients with a vascular access].

Patients undergoing haemodialytic treatment have a lower quality of life than the general population because of several factors. Their wellbeing can be assessed through a clinical evaluation or through the subjective point of view of the patients themselves: the perceived Health-Related Quality of Life (HRQoL) is an index calculated on the basis of the patients' own perspective. A well-functioning vascular access (VA) and the absence of complications are certainly associated with better health in patients on dialysis but unfortunately VA-related perceived HRQoL has so far been a subject of little interesting literature, even though the choice of the most appropriate access in the individual patient is today increasingly articulate and difficult. Information about subjective perception of health is typically collected through generic or specific questionnaires. The most used reproducible questionnaires available are SF-36, EuroQoL5D, SONG-HD, WHOQoL-BREF, VAQ, although not all of them have been used for a targeted assessment of the issues concerning HRQoL and VA function. This review confirms that the VAQ questionnaire is currently the simplest and most reliable tool to assess patient satisfaction with their VA.

The Mad1/Mad2 complex as a template for Mad2 activation in the spindle assembly checkpoint.

BACKGROUND: The spindle assembly checkpoint (SAC) imparts fidelity to chromosome segregation by delaying anaphase until all sister chromatid pairs have become bipolarly attached. Mad2 is a component of the SAC effector complex that sequesters Cdc20 to halt anaphase. In prometaphase, Mad2 is recruited to kinetochores with the help of Mad1, and it is activated to bind Cdc20. These events are linked to the existence of two distinct conformers of Mad2: a closed conformer bound to its kinetochore receptor Mad1 or its target in the checkpoint Cdc20 and an open conformer unbound to these ligands. RESULTS: We investigated the mechanism of Mad2 recruitment to the kinetochore during checkpoint activation and subsequent transfer to Cdc20. We report that a closed conformer of Mad2 constitutively bound to Mad1, rather than Mad1 itself, is the kinetochore receptor for cytosolic open Mad2 and show that the interaction of open and closed Mad2 conformers is essential to sustain the SAC. CONCLUSIONS: We propose that closed Mad2 bound to Mad1 represents a template for the conversion of open Mad2 into closed Mad2 bound to Cdc20. This simple model, which we have named the "Mad2 template" model, predicts a mechanism for cytosolic propagation of the spindle checkpoint signal away from kinetochores.

[Clinical practice for the diagnosis of cardiac arrhythmias in patients on renal replacement therapy: data from a Lombard survey]. / Pratica clinica per la diagnostica delle aritmie cardiache in pazienti in terapia renale sostitutiva: dati di una survey lombarda.

Among dialysis patients, 40% of deaths are due to cardiovascular causes, and 60% of cardiac deaths are due to an arrhythmia. The purpose of this survey, carried out with the organizational support of the Lombard Section of the Italian Society of Nephrology, is to evaluate the frequency and mode of use of non-invasive instruments for the diagnosis of cardiac arrhythmias in the dialysis centers of Lombardy. Information on the prevalence and type of cardiac devices at December 1, 2016 in this population was also required. Data from 18 centers were collected for a total of 3395 patients in replacement renal therapy, including 2907 (85.6%) in hemodialysis and 488 (14.4%) in peritoneal dialysis. All centers use the 12-lead ECG in case of evocative symptoms of an arrhythmic event and 2/3 perform the exam with programmed cadence (usually once a year). Twenty four-hour ECG Holter is not used as a routine diagnostic tool. The proportion of cardiac devices is relatively high, compared to literature data: n=259, equal to 7.6% of the population. Pace-Maker patients are 166 (4.9%), those with intracardiac defibrillator 52 (1.5%), those with resynchronization therapy 18 (0.5%) and those with resynchronization therapy and intracardiac defibrillator 23 (0.7%). The survey provides interesting information and can be an important starting point for trying to optimize clinical practice and collaboration between nephrologists and cardiologists in front of a major problem like that of arrhythmic disease in patients on renal replacement therapy.

Hypertension, prehypertension, and transient elevated blood pressure in children: association with weight excess and waist circumference.

BACKGROUND: To assess the prevalence of hypertension (H), prehypertension (PH), and transient elevated blood pressure (TH) and their relationship with weight class and waist circumference (WC) in an unselected population of Northern Italian children. METHODS: A cross-sectional study was conducted in 5,131 children (5-11 years). Weight class was defined according to the International Obesity Task Force references, H and PH according to the National High Blood Pressure Education Program. A child was classified as having PH or H when systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) at first screening were > or =90th percentile and the mean of three subsequent measures was between the 90th and 95th or > or =95th percentile, respectively. When BP values at the first screening were > or =90th percentile but the mean of three subsequent measures was <90th percentile the child was classified as having TH. RESULTS: A proportion of 3.4% presented H, 2.7% PH, and 10.4% TH, 20% overweight, and 6% obesity. Weight class and WC were significantly associated to an increased risk of falling into any of the hypertensive categories. In children with TH BP z-scores of the mean of the three subsequent measurements following the first screening were significantly higher than BP z-scores observed in normotensive children (P value <0.001). CONCLUSIONS: Weight class and WC are associated with BP. This is observed not only for H but also for PH, and for nonsustained forms of H. Prospective studies are needed to assess whether children with PH and TH will develop sustained H.

Clinical evidence continuous medical education: a randomised educational trial of an open access e-learning program for transferring evidence-based information - ICEKUBE (Italian Clinical Evidence Knowledge Utilization Behaviour Evaluation) - study protocol.

BACKGROUND: In an effort to ensure that all physicians have access to valid and reliable evidence on drug effectiveness, the Italian Drug Agency sponsored a free-access e-learning system, based on Clinical Evidence, called ECCE. Doctors have access to an electronic version and related clinical vignettes. Correct answers to the interactive vignettes provide Continuing Medical Education credits. The aims of this trial are to establish whether the e-learning program (ECCE) increases physicians' basic knowledge about common clinical scenarios, and whether ECCE is superior to the passive diffusion of information through the printed version of Clinical Evidence. DESIGN: All Italian doctors naïve to ECCE will be randomised to three groups. Group one will have access to ECCE for Clinical Evidence chapters and vignettes lot A and will provide control data for Clinical Evidence chapters and vignettes lot B; group two vice versa; group three will receive the concise printed version of Clinical Evidence. There are in fact two designs: a before and after pragmatic trial utilising a two by two incomplete block design (group one versus group two) and a classical design (group one and two versus group three). The primary outcome will be the retention of Clinical Evidence contents assessed from the scores for clinical vignettes selected from ECCE at least six months after the intervention. To avoid test-retest effects, we will randomly select vignettes out of lot A and lot B, avoiding repetitions. In order to preserve the comparability of lots, we will select vignettes with similar, optimal psychometric characteristics.

Explaining the oligomerization properties of the spindle assembly checkpoint protein Mad2.

Mad2 is an essential component of the spindle assembly checkpoint (SAC), a molecular device designed to coordinate anaphase onset with the completion of chromosome attachment to the spindle. Capture of chromosome by microtubules occur on protein scaffolds known as kinetochores. The SAC proteins are recruited to kinetochores in prometaphase where they generate a signal that halts anaphase until all sister chromatid pairs are bipolarly oriented. Mad2 is a subunit of the mitotic checkpoint complex, which is regarded as the effector of the spindle checkpoint. Its function is the sequestration of Cdc20, a protein required for progression into anaphase. The function of Mad2 in the checkpoint correlates with a dramatic conformational rearrangement of the Mad2 protein. Mad2 adopts a closed conformation (C-Mad2) when bound to Cdc20, and an open conformation (O-Mad2) when unbound to this ligand. Checkpoint activation promotes the conversion of O-Mad2 to Cdc20-bound C-Mad2. We show that this conversion requires a C-Mad2 template and we identify this in Mad1-bound Mad2. In our proposition, Mad1-bound C-Mad2 recruits O-Mad2 to kinetochores, stimulating Cdc20 capture, implying that O-Mad2 and C-Mad2 form dimers. We discuss Mad2 oligomerization and link our discoveries to previous observations related to Mad2 oligomerization.