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Background To date, only twenty-one cases diagnosed postnatally with mosaic trisomy 12 have been reported. The most frequent phenotypic manifestations are developmental delay, dysmorphic facial features, congenital heart defects, digital alterations, and pigmentary disorders. In the present report, detailed clinical and genetic profiles of three unrelated new patients with mosaic trisomy 12 are described and compared with previously reported cases. Case presentation In the present report, we include the clinical, cytogenetic, and molecular description of three Mexican patients diagnosed postnatally with mosaic trisomy 12. At phenotypic level, the three patients present with developmental delay, dysmorphic facial features, congenital heart defects and skin pigmentary anomalies. Particularly, patient 1 showed unique eye alterations as bilateral distichiasis, triple rows of upper lashes, and digital abnormalities. In patient 2 redundant skin, severe hearing loss, and hypotonia were observed, and patient 3 presented with hypertelorism and telecanthus. Hyperpigmentation with disseminated pigmentary anomalies is a common trait in all of them. The cytogenetic study was carried out under the strict criteria of analysis, screening 50–100 metaphases from three different tissues, showing trisomy 12 mosaicism in at least one of the three different tissues analyzed. With SNParray, the presence of low-level mosaic copy number variants not previously detected by cytogenetics, and uniparental disomy of chromosome 12, was excluded. STR markers allowed to confirm the absence of uniparental disomy as well as to know the parental origin of supernumerary chromosome 12. Conclusions The detailed clinical, cytogenetic, and molecular description of these three new patients, contributes with relevant information to delineate more accurately a group of patients that show a heterogeneous phenotype, although sharing the same chromosomal alteration. The possibility of detecting mosaic trisomy 12 is directly associated with the sensitivity of the methodology applied to reveal the low-level chromosomal mosaicism, as well as with the possibility to perform the analysis in a suitable tissue.

The cardiovascular disease pandemic has promoted the cardiovascular polypill as one of the most scalable public health strategies to improve cardiovascular risk by increasing accessibility and adherence to treatments. Data from randomized clinical trials has shown that the polypill strategy significantly improves adherence as well as risk factor control (cholesterol and blood pressure), however, to date, no information from phase IV registries has been available.We conducted a multicentre, observational and prospective registry of a polypill-based treatment strategy. A total of 1193 patients in Mexico were included. Patient demographics, clinical history, blood pressure, analysis of blood lipids and the Framingham risk score were measured at baseline and after 12 months of treatment with the CNIC-Ferrer polypill.At one year with the polypill, systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels changed from mean 146.9 mmHg to 128 mmHg (p 0.001), and from 89.1 mmHg to 80.4 mmHg (p 0.001) respectively. LDLc levels were significantly reduced 132.5-107.6 mg/dL (p 0.001). The 10 year Framingham cardiovascular disease risk was also reduced in the high-risk group (33.7 + 22.0 vs. 21.2 + 14.8; p 0.001) and in the intermediate risk group (23.7 + 14.8 vs. 12.7 + 11.4; p 0.001).To our knowledge, the results of the current study constitute the first real life data on the impact of a polypill therapy on cardiovascular risk factor control. The results show major improvements on the primary outcome, above and beyond those presented previously in the setting of randomized clinical trials.

Glycation is initiated by reaction of a reducing sugar with a protein amino group to generate a Schiff base adduct. Following an Amadori rearrangement to form a ketoamine adduct, a complex chemistry involving oxidation often leads to protein glycoxidation products referred to as advanced glycosylation end products (AGE). The AGE include protein carboxymethyllysine (CML) residues and a heterogeneous group of complex modifications characterized by high fluorescence and protein-protein cross links. The sugar sources for the glycoxidation of intracellular proteins are not well defined but pentoses have been implicated because they are efficient precursors for the formation of the fluorescent AGE, pentosidine. ADP-ribose, generated from NAD by ADP-ribose transfer reactions, is a likely intracellular source of a reducing pentose moiety. Incubation of ADP-ribose with histones results in the formation of ketoamine glycation conjugates and also leads to the rapid formation of protein CML residues, histone H1 dimers, and highly fluorescent products with properties similar to the AGE. ADP-ribose is much more efficient than other possible pentose donors for glycation and glycoxidation of protein amino groups. Recently developed methods that differentiate nonenzymic modifications of proteins by ADP-ribose from enzymic modifications now allow investigations to establish whether some protein modifications by monomers of ADP-ribose in vivo represent glycation and glycoxidation.

Cyclic ADP-ribose is a recently discovered metabolite of NAD that functions in cellular calcium signalling. The discovery that NAD glycohydrolases can catalyze the synthesis and hydrolysis of cyclic ADP-ribose has renewed interest in this class of ADP-ribose transferring enzymes that were discovered over 50 years ago.

Anticoagulant therapy in the treatment of cerebral thromboembolism remains controversial despite 20 years of statistical studies. Among the unresolved questions are (1) the relative value of aspirin vs coumarin derivatives for long-term therapy; (2) the relative benefits of long-term therapy vs short-term therapy; (3) the complications of anticoagulant therapy vs their therapeutic benefits; and (4) the optimal therapy of the various types of cerebral thromboembolic events, eg, transient ischemic attacks, strokes in evolution, and completed strokes. Much of this controversy derives from the same problems that have plagued the question of anticoagulation for acute myocardial infarction, namely that "the existing statistics were obtained without adequate attention to fundamental principles of clinical science". We have examined the available clinical studies bearing on this issue and are reporting our analysis of these studies.

We studied 13 patients with acute attacks of asthma to test the hypothesis that magnitude of dyspnea at rest correlates well with spirometry and with breath-holding time. Dyspnea ("falta de aire" in Spanish) was quantitated with a linear numerical scale from 0 to 10. We measured breath-holding time, breathing frequency (f), and FEV1 and FVC both expressed as percent of normal. Measurements were done on the patient's arrival and were repeated 3 to 6 times until dyspnea at rest disappeared or was minimal. Dyspnea magnitude, f, and breath-holding time correlated well with FEV1% and FVC% (r between 0.65 and 0.78), and better with changes in FEV1% and FVC% with respect to initial values (delta FEV1 y delta FVC; r between 0.80 and 0.89). Breath-holding time and f changed in proportion to magnitude of dyspnea (r = -0.85 and 0.87 respectively). Regression equations were: dyspnea = 6.34 -0.16 (delta FEV1) r = 0.80, and dyspnea = 7.82-0.105 (FEV1%) r = 0.62. Using multiple regression we improved prediction of FEV1% with easily obtained variables (R = 0.76). These results suggest that: 1) magnitude of dysnea, f, and breath-holding time correlate with severity of airflow obstruction in acute asthma attacks associated with dyspnea at rest; and 2) breath-holding time varies inversely with dyspnea magnitude when it is present at rest.

We utilized a combined, hormonal-stimulation test (CHST) using sequentially-administered insulin, thyrotropin-releasing hormone, gonadotropin-releasing hormone, and levodopa to assess 51 children with short stature and/or pathologic growth. Growth hormone, thyrotropin, gonadotropins, cortisol, and prolactin levels were sampled over two hours. All patients with appropriate predicted adult heights, delayed bone ages, and normal growth velocities of 4.0 cm/y or greater demonstrated normal pituitary responses. Two of 12 patients with predicted heights 2.5 SDs lower than target height and normal growth velocity demonstrated isolated growth hormone deficiency. Nine of 11 patients had a pathologic growth hormone deficiency or panhypopituitarism. Evaluation of pituitary function by combined sequential hormonal stimulation is fruitful in children with pathologic growth patterns but not in children with normal growth velocities and normal predicted adult height.