50 research outputs found

    Tripodal O-N-O bis-Phenolato Amine Titanium(IV) Complexes Show High In Vitro Anti-Cancer Activity

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    The octahedral titanium(IV) complexes trans,mer‐[Ti{R3N(CH2C6H2‐2‐O‐4‐R2‐6‐R1)2}2] (R1 = Me, OMe, Cl; R2 = Me, OMe, F, Cl; R3 = Me, Et; not all combinations) are synthesised in two steps from simple phenols in 36‐53% overall yield. The highly crystalline (4 X‐ray structures) complexes are active against MCF‐7 (breast) and HCT‐116 (colon) cancer cell lines showing widely varying GI50 values in the range 1‐100 ”M depending on R1‐R3. Highest activities are realised when R1 = OMe and R2, R3 = Me (GI50 ~1 ”M for MCF‐7 and 2‐3 ”M for HCT‐116). These are respectively 8× and 3× times greater than the activities of cisplatin in the same cell lines. These titanium complexes show some significant selectivity for cancer cell lines; up to 7× higher in MCF‐7 compared to non‐cancer (MRC‐5) fibroblast cells. Details of cellular mode of action indicators (cell cycle perturbation, Annexin V, γ‐H2AX, and caspase studies) that point to an apoptosis mode for the most active compound (R1 = OMe and R2, R3 = Me) are also reported

    Frecuencia de mutaciones encontradas en niños con enfermedad renal crónica por síndrome nefrótico cortico-resistente

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    Chronic kidney disease in children may be caused by a group of genetic abnormalities of the kidney, urinary tract and hereditary nephropathies. Objective: To report the frequency of mutations in children with steroid-resistant nephrotic syndrome (SRNS). Methods: A multicentric case series among children with SRNS identified through direct sequencing of NPHS1, NPHS2, NPHP1 and WT1 genes. Results: 33 children were enrolled; 45.5% were females; mean age was 13±7 years; 78.8% were mestizo: 24.2% consanguineous; 60.6% were receiving dialysis: 72.7% had SRNS and 8/24 (33.3%) of them presented at least one mutation to WT1, NPHS1, NPHP1 and NPHS2 genes. Corresponding values for these mutations were 37.5% (3/8), 25% (2/8), 25% (2/8) and 12.5% (1/8), respectively. Conclusions: 33% of pediatric patients with SRNS presented gene mutations, the most frequent of these mutations was WT1.La enfermedad renal crĂłnica en niños puede tener como etiologĂ­a un grupo cuya causa genĂ©tica, incluye las anomalĂ­as congĂ©nitas del riñón y las vĂ­as urinarias y las nefropatĂ­as hereditarias. Objetivo: Describir la frecuencia de mutaciones en niños con sĂ­ndrome nefrĂłtico corticoresistente (SNRE). Material y mĂ©todos: Estudio multicĂ©ntrico, tipo serie de casos, realizado en niños con SNRE, mediante el resultado de secuenciamiento directo de los genes; NPHS1, NPHS2, NPHP1 y WT1. Resultados: Se enrolaron 33 pacientes pediĂĄtricos con enfermedad renal crĂłnica, 45,5% mujeres, edad promedio 13±7 años, 78,8% de raza mestiza, 24,2% consanguĂ­neos, 60,6% se encontraban en hemodiĂĄlisis, 72,7% presentaban sĂ­ndrome nefrĂłtico cortico resistente y de ellos 8/24 (33,3%) presentĂł al menos una mutaciĂłn en los genes; WT1, NPHS1, NPHP1y NPHS2 siendo la frecuencia de estas mutaciones de 37,5% (3/8), 25% (2/8), 25% (2/8) y 12,5% (1/8), respectivamente.  Conclusiones: El 33,3% de los pacientes pediĂĄtricos con enfermedad renal crĂłnica con sĂ­ndrome nefrĂłtico corticoresistente (SNRE) presentaron mutaciones, la mĂĄs frecuente fue en el gen WT1

    Developmental Reaction Norms for Water Stressed Seedlings of Succulent Cacti

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    Succulent cacti are remarkable plants with capabilities to withstand long periods of drought. However, their adult success is contingent on the early seedling stages, when plants are highly susceptible to the environment. To better understand their early coping strategies in a challenging environment, two developmental aspects (anatomy and morphology) in Polaskia chichipe and Echinocactus platyacanthus were studied in the context of developmental reaction norms under drought conditions. The morphology was evaluated using landmark based morphometrics and Principal Component Analysis, which gave three main trends of the variation in each species. The anatomy was quantified as number and area of xylem vessels. The quantitative relationship between morphology and anatomy in early stages of development, as a response to drought was revealed in these two species. Qualitatively, collapsible cells and collapsible parenchyma tissue were observed in seedlings of both species, more often in those subjected to water stress. These tissues were located inside the epidermis, resembling a web of collapsible-cell groups surrounding turgid cells, vascular bundles, and spanned across the pith. Occasionally the groups formed a continuum stretching from the epidermis towards the vasculature. Integrating the morphology and the anatomy in a developmental context as a response to environmental conditions provides a better understanding of the organism's dynamics, adaptation, and plasticity

    Comprehensive description of clinical characteristics of a large systemic Lupus Erythematosus Cohort from the Spanish Rheumatology Society Lupus Registry (RELESSER) with emphasis on complete versus incomplete lupus differences

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    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement and pronounced racial and ethnic heterogeneity. The aims of the present work were (1) to describe the cumulative clinical characteristics of those patients included in the Spanish Rheumatology Society SLE Registry (RELESSER), focusing on the differences between patients who fulfilled the 1997 ACR-SLE criteria versus those with less than 4 criteria (hereafter designated as incomplete SLE (iSLE)) and (2) to compare SLE patient characteristics with those documented in other multicentric SLE registries. RELESSER is a multicenter hospital-based registry, with a collection of data from a large, representative sample of adult patients with SLE (1997 ACR criteria) seen at Spanish rheumatology departments. The registry includes demographic data, comprehensive descriptions of clinical manifestations, as well as information about disease activity and severity, cumulative damage, comorbidities, treatments and mortality, using variables with highly standardized definitions. A total of 4.024 SLE patients (91% with ≄4 ACR criteria) were included. Ninety percent were women with a mean age at diagnosis of 35.4 years and a median duration of disease of 11.0 years. As expected, most SLE manifestations were more frequent in SLE patients than in iSLE ones and every one of the ACR criteria was also associated with SLE condition; this was particularly true of malar rash, oral ulcers and renal disorder. The analysis-adjusted by gender, age at diagnosis, and disease duration-revealed that higher disease activity, damage and SLE severity index are associated with SLE [OR: 1.14; 95% CI: 1.08-1.20 (P < 0.001); 1.29; 95% CI: 1.15-1.44 (P < 0.001); and 2.10; 95% CI: 1.83-2.42 (P < 0.001), respectively]. These results support the hypothesis that iSLE behaves as a relative stable and mild disease. SLE patients from the RELESSER register do not appear to differ substantially from other Caucasian populations and although activity [median SELENA-SLEDA: 2 (IQ: 0-4)], damage [median SLICC/ACR/DI: 1 (IQ: 0-2)], and severity [median KATZ index: 2 (IQ: 1-3)] scores were low, 1 of every 4 deaths was due to SLE activity. RELESSER represents the largest European SLE registry established to date, providing comprehensive, reliable and updated information on SLE in the southern European population

    GuĂ­a de prĂĄctica clĂ­nica para el manejo de la Enfermedad Renal CrĂłnica estadĂ­os 3b, 4 y 5 en el Seguro Social de Salud del PerĂș (EsSalud)

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    Introduction: This article summarizes the clinical practice guideline (CPG) for the management of stage 3b, 4, and 5 chronic kidney disease (CKD) in the Social Security of Peru (EsSalud). Objective: To provide evidence-based clinical recommendations for the management of stage 3b, 4, and 5 CKD in EsSalud. Methods: A guideline development group (GDG) was formed, including specialists and methodologists. The GDG formulated 9 clinical questions. Systematic searches for systematic reviews and primary studies were conducted in PubMed from December 2020 to August 2021. Evidence was selected to answer the clinical questions posed. The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The GDG used the GRADE methodology to review the evidence and formulate recommendations, points of good clinical practice (GPC), and management flowcharts. Finally, the CPG was approved with Resolution No. 88-IETSI-ESSALUD-2021. Results: This CPG addressed 9 clinical questions. Based on these questions, 17 recommendations (7 strong and 10 conditional), 28 GPC points, and 4 management flowcharts were formulated. Conclusion: This article summarizes the methodology and evidence-based conclusions of the CPG for the management of stage 3b, 4, and 5 CKD in EsSalud.IntroducciĂłn: El presente artĂ­culo resume la guĂ­a de prĂĄctica clĂ­nica (GPC) para el manejo de la enfermedad renal crĂłnica estadĂ­os 3b, 4 y 5 en el Seguro Social del PerĂș (EsSalud). Objetivo: Proveer recomendaciones clĂ­nicas basadas en evidencia para el manejo de pacientes con enfermedad renal crĂłnica estadĂ­os 3b, 4 y 5 en EsSalud. MĂ©todos: Se conformĂł un grupo elaborador de la guĂ­a (GEG) que incluyĂł especialistas y metodĂłlogos. El GEG formulĂł 9 preguntas clĂ­nicas. Se realizĂł bĂșsquedas sistemĂĄticas de revisiones sistemĂĄticas y estudios primarios en PubMed entre diciembre del 2020 y agosto del 2021. Se seleccionĂł la evidencia para responder a las preguntas clĂ­nicas planteadas. La certeza de la evidencia fue evaluada usando la metodologĂ­a Grading of Recommendations Assessment, Development, and Evaluation (GRADE). El GEG usĂł la metodologĂ­a GRADE para revisar la evidencia y formular recomendaciones, los puntos de buena prĂĄctica clĂ­nica (BPC) y los flujogramas de manejo. Finalmente, la GPC fue aprobada con ResoluciĂłn N° 88-IETSI-ESSALUD-2021. Resultados: La presente GPC abordĂł 9 preguntas clĂ­nicas. En base a dichas preguntas se formularon 17 recomendaciones (7 fuertes y 10 condicionales), 28 BPC, y 4 flujogramas de manejo. ConclusiĂłn: El presente artĂ­culo resume la metodologĂ­a y las conclusiones basadas en evidencias de la GPC para el manejo de la Enfermedad Renal CrĂłnica estadĂ­os 3b, 4 y 5 en EsSalud

    Impact of preemptive hospitalization on health outcomes at the temporary COVID-19 hospital in Mexico City: a prospective observational study.

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    INTRODUCTION: In response to the evolution of the coronavirus disease 2019 (COVID-19) pandemic, the admission protocol for the temporary COVID-19 hospital in Mexico City has been updated to hospitalize patients preemptively with an oxygen saturation (SpO2) of >90%. METHODS: This prospective, observational, single-center study compared the progression and outcomes of patients who were preemptively hospitalized versus those who were hospitalized based on an SpO2 ⩜90%. We recorded patient demographics, clinical characteristics, COVID-19 symptoms, and oxygen requirement at admission. We calculated the risk of disease progression and the benefit of preemptive hospitalization, stratified by CALL Score: age, lymphocyte count, and lactate dehydrogenase (<8 and ⩟8) at admission. RESULTS: Preemptive hospitalization significantly reduced the requirement for oxygen therapy (odds ratio 0.45, 95% confidence interval 0.31-0.66), admission to the intensive care unit (ICU) (0.37, 0.23-0.60), requirement for invasive mechanical ventilation (IMV) (0.40, 0.25-0.64), and mortality (0.22, 0.10-0.50). Stratification by CALL score at admission showed that the benefit of preemptive hospitalization remained significant for patients requiring oxygen therapy (0.51, 0.31-0.83), admission to the ICU (0.48, 0.27-0.86), and IMV (0.51, 0.28-0.92). Mortality risk remained significantly reduced (0.19, 0.07-0.48). CONCLUSION: Preemptive hospitalization reduced the rate of disease progression and may be beneficial for improving COVID-19 patient outcomes

    Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

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    BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

    Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

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    BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

    Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

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    BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

    Odontología Legal y Ética - OD196 - 202102

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    DESCRIPCIÓN: El curso de OdontologĂ­a Legal y Ética es un curso Blended teĂłrico Âż prĂĄctico que pertenece al bloque de cursos electivos de la carrera de odontologĂ­a, donde aplica los fundamentos legales y Ă©ticos de la prĂĄctica odontolĂłgica. Asimismo, los estudiantes conocerĂĄn los principios de los cĂłdigos de procesos penales, civiles, como tambiĂ©n la ConstituciĂłn PolĂ­tica del PerĂș y el manejo bĂĄsico de un negocio odontolĂłgico desde una perspectiva legal
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