Farmacología de la nicotina y sus efectos en el sistema nervioso central.

capitulo del libroLos niveles más altos de nicotina en sangre se alcanzan al terminar de fumar un cigarrillo y declinan rápidamente en los siguientes 20 minutos por la amplia distribución en los tejidos corporales. El volumen de distri- bución en humanos es 2.6 veces el peso corporal (Rose et al., 1999). La nicotina es metabolizada por el hígado y se han identificado al menos seis metabolitos primarios, siendo cuantitativamente el más importante la cotinina. Otros metabolitos primarios son la nicotina-N-óxido y el glu- curónido de nicotina. Los metabolitos de cotinina son los siguientes: glu- curónido de cotinina, trans-3-hidroxicotinina y glucurónido trans-3-hi- droxicotininaconacy

Desarrollo municipal. Una visión contemporánea

Para los estudiosos y el público interesado en los asuntos municipales, 2013 fue un año emblemático porque se cumplieron tres décadas de la reforma al artículo 115 constitucional, precepto que sustancia la vida institucional de los municipios mexicanos. La vida municipal, merced a este periodo, se ha revitalizado, aunque de manera diferenciada entre caso y caso, pues la heterogeneidad económica, política y social persiste, así como sus efectos adversos, sobre los municipios más rezagados; ello es recordatorio de las deudas pendientes del Estado con esta expresión local. Tal revitalización ha alcanzado a la discusión académica con un resultado exuberante en producción editorial que da cuenta de significativos cambios en la vida asociada

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Imperceptible–Visible Watermarking to Information Security Tasks in Color Imaging

Digital image watermarking algorithms have been designed for intellectual property, copyright protection, medical data management, and other related fields; furthermore, in real-world applications such as official documents, banknotes, etc., they are used to deliver additional information about the documents’ authenticity. In this context, the imperceptible–visible watermarking (IVW) algorithm has been designed as a digital reproduction of the real-world watermarks. This paper presents a new improved IVW algorithm for copyright protection that can deliver additional information to the image content. The proposed algorithm is divided into two stages: in the embedding stage, a human visual system-based strategy is used to embed an owner logotype or a 2D quick response (QR) code as a watermark into a color image, maintaining a high watermark imperceptibility and low image-quality degradation. In the exhibition, a new histogram binarization function approach is introduced to exhibit any watermark with enough quality to be recognized or decoded by any application, which is focused on reading QR codes. The experimental results show that the proposed algorithm can embed one or more watermark patterns, maintaining the high imperceptibility and visual quality of the embedded and the exhibited watermark. The performance evaluation shows that the method overcomes several drawbacks reported in previous algorithms, including geometric and image processing attacks such as JPEG and JPEG2000

Performance of a Nanofluid-Cooled Segmented Thermoelectric Generator: Hollow/Filled Leg Structures and Segmentation Effects

A thermoelectric generator (TEG) is studied by considering different leg structures of hollow/filled legs, using new cooling nanofluids, and analyzing the segmentation effect. TEG performance is characterized by power output, conversion efficiency, and exergy efficiency. This study shows the impact of different cooling nanofluids (TiO2, graphene, and Al2O3) on the performance of the thermoelectric generator. Furthermore, in the comparative analysis of nanofluid cooling enhancement for TEG, different hollow/filled thermoelectric legs recently proposed in the literature are considered. Likewise, three segmentation types are used, 2n-2p, 1n-2p, and 2n-1p, thus will be compared with the results of the unsegmented legs. This study calculates the performance of thermoelectric leg structures through a validated numerical simulation on the ANSYS Workbench (modeling, design, and simulation). In addition, the optimal working conditions are evaluated. This study found that quenching of nanofluids can improve TEG performance by up to 17% compared to distilled water. However, the performance improvement of the TEG for each nanofluid is small between them. Furthermore, segmentation of n-type thermocouples improves efficiency and exergy, whereas segmentation of p-type thermocouples improves output power. The segmentation enhances performance by up to twice that of non-segmented leg structures; hollow structures are better performers. In the results, it is reported that the 2n-1p segmentation is the one with the best performance, reaching a maximum energy efficiency of 38%. The triangular leg structure improves performance by up to 75% compared to the rectangular and square leg structures. Likewise, using TiO2 is the best cooling option with nanofluids since it improves performance by 17% compared to distilled water. Furthermore, the results of cooling nanofluids for TEG performance are useful for the design of thermoelectric leg structures and stimulate further research

A New Approach for Approximate Solution of ADE: Physical-Based Modeling of Carriers in Doping Region

The electric behavior in semiconductor devices is the result of the electric carriers’ injection and evacuation in the low doping region, N-. The carrier’s dynamic is determined by the ambipolar diffusion equation (ADE), which involves the main physical phenomena in the low doping region. The ADE does not have a direct analytic solution since it is a spatio-temporal second-order differential equation. The numerical solution is the most used, but is inadequate to be integrated into commercial electric circuit simulators. In this paper, an empiric approximation is proposed as the solution of the ADE. The proposed solution was validated using the final equations that were implemented in a simulator; the results were compared with the experimental results in each phase, obtaining a similarity in the current waveforms. Finally, an advantage of the proposed methodology is that the final expressions obtained can be easily implemented in commercial simulators

El municipio mexicano ante los grandes retos del siglo XXI

Las transformaciones económicas, políticas y sociales que caracterizan a nuestro país en la ya avanzada segunda década del siglo XXL están vinculadas al contexto histórico endógeno y de manera creciente al exógeno, en este caso, en la medida en que la interdependencia, la globalización y la mundialización avanzan, y no sería exagerado que también lo estén a los escenarios prospectivos, toda vez que las premisas del futuro inmediato y de mediano plazo en buena medida ya están sentadas; difícilmente podríamos aspirar a un futuro promisorio y de lata calidad de vida si no procedemos con acciones políticas y estrategias orientadas en ese sentido; de igual manera, actualmente recibimos los beneficios, aunque también nos vemos desfavorecidos y padecemos por el conjunto de premisas, omisiones, excesos y políticas erróneas que se establecieron en los años y décadas pasadas en nuestro contexto histórico

Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1):24 week results from a multicentre, double-blind, phase 3, randomised controlled trial

Background Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor approved for the treatment of type 2 diabetes. We aimed to assess the efficacy and safety of dapagliflozin as an add-on to adjustable insulin in patients with inadequately controlled type 1 diabetes. Methods DEPICT-1 was a double-blind, randomised, parallel-controlled, three-arm, phase 3, multicentre study done at 143 sites in 17 countries. Eligible patients were aged 18–75 years and had inadequately controlled type 1 diabetes (HbA1cbetween ≥7·7% and ≤11·0% [≥61·0 mmol/mol and ≤97·0 mmol/mol]) and had been prescribed insulin for at least 12 months before enrolment. After an 8 week lead-in period to optimise diabetes management, patients were randomly assigned (1:1:1) using an interactive voice response system to dapagliflozin 5 mg or 10 mg once daily, given orally, or matched placebo. Randomisation was stratified by current use of continuous glucose monitoring, method of insulin administration, and baseline HbA1c. The primary efficacy outcome was the change from baseline in HbA1cafter 24 weeks of treatment in the full analysis set, which consisted of all randomly assigned patients who received at least one dose of study drug. An additional 55 patients who were incorrectly and non-randomly allocated to only dapagliflozin treatment groups were included in the safety analysis set. This study was registered with ClinicalTrials.gov, number NCT02268214; data collection for the present analysis was completed on Jan 4, 2017, and a 28 week extension phase is ongoing. Findings Between Nov 11, 2014, and April 16, 2016, 833 patients were assigned to treatment groups and included in safety analyses (dapagliflozin 5 mg [n=277] vs dapagliflozin 10 mg [n=296] vs placebo [n=260]; 778 of these patients were randomly assigned and included in the full analysis set for efficacy analyses (259 vs 259 vs 260; difference due to randomisation error affecting 55 patients). Mean baseline HbA1cwas 8·53% (70 mmol/mol; SD 0·67% [7·3 mmol/mol]). At week 24, both doses of dapagliflozin significantly reduced HbA1ccompared with placebo (mean difference from baseline to week 24 for dapagliflozin 5 mg vs placebo was −0·42% [95% CI −0·56 to −0·28; p&lt;0·0001] and for dapagliflozin 10 mg vs placebo was −0·45% [−0·58 to −0·31; p&lt;0·0001]). Among patients in the dapagliflozin 5 mg (n=277), dapagliflozin 10 mg (n=296), and placebo (n=260) groups, the most common adverse events were nasopharyngitis (38 [14%] vs 36 [12%] vs 39 [15%]), urinary tract infection (19 [7%] vs 11 [4%] vs 13 [5%]), upper respiratory tract infection (15 [5%] vs 15 [5%] vs 11 [4%]), and headache (12 [4%] vs 17 [6%] vs 11 [4%]). Hypoglycaemia occurred in 220 (79%), 235 (79%), and 207 (80%) patients in the dapagliflozin 5 mg, dapagliflozin 10 mg, and placebo groups, respectively; severe hypoglycaemia occurred in 21 (8%), 19 (6%), and 19 (7%) patients, respectively. Adjudicated definite diabetic ketoacidosis occurred in four (1%) patients in the dapagliflozin 5 mg group, five (2%) in the dapagliflozin 10 mg group, and three (1%) in the placebo group. Interpretation Our results suggest that dapagliflozin is a promising adjunct treatment to insulin to improve glycaemic control in patients with inadequately controlled type 1 diabetes. Funding AstraZeneca and Bristol-Myers Squibb